Current Topics in Medicinal Chemistry

Burgeoning rise in different disease cases such as cancer, viral diseases including Dengue, Chikungunya, Zika, Ebola, Japanese encephalitis, etc., other tropical and neglected diseases, metabolic conditions such as diabetes and many other health conditions warrants the need of immediate investigations and end the human plight for ensuring a better tomorrow. Advances in scientific research have shown the impact in eradication and prevention of many diseases conditions such as polio. Interplay of experimental and theoretical approaches have come a long way in proving their effectiveness and worth in this regard. Earlier computational approaches were almost ignored by a large section of the scientific community. Last few decades have witnessed a drastic change in the existing beliefs and today theoretical techniques are not only supporting and supplementing experimental results but also guiding studies by providing valuable cues. Computational approaches pertaining to understanding complex biological system have come a long way during past few years rising from its infancy to blooming into a full-fledged science. Simple bioinformatics and chemo-informatics approaches are being frequently applied in the arena of system biology and are providing remarkable insights on unsolved and unanswered scientific questions so far.

Battling diseases requires concerted efforts towards innovation and discovery. In today’s world and time, we face unprecedented challenges of organizing and prioritizing our strategies against diseases. Development of effective and commercially feasible therapeutic agents or drugs is a time consuming and labour–intensive process which thrives on an array of resources. It is assumed that application of Computer Aided Drug Design (CADD) for prospecting and profiling of new lead compounds in initial stages of drug discovery pipeline will offer many advantages both in terms of monetary gain and optimal use of available resources. Computational chemistry, a combinatorial subject has come a long way from its initial days of being considered as an auxiliary science to an indispensable part of most modern drug developmental programs. As the trend shifted from one gene or protein approach towards the whole genome or proteome analysis in unveiling disease mechanism and progression, computational approaches slowly but steadily made their way in domain once owned exclusively by medicinal chemists or biologists. The field has grown by leaps and bounds not only because of advances in computational technology, software development and processing speed but also because of mammoth scale and rapid pace of generation of experimentally derived data and myriad types of data available waiting to be analyzed and used. Computational approaches are touching all realms of life and have catapulted to a position where their crucial role in generating and validating hypotheses, disease identification, knowledge discovery, therapeutics and control by identification of novel drug targets, drug molecules and vaccines cannot be denied. Some of the well known applications of computational approaches in drug designing include structure elucidation by molecular modeling, Quantitative Structure-Activity Relationships (QSAR), docking and molecular simulation, toxicity prediction, machine learning and data mining approaches for data analysis and visualization. Considering the huge risks of reemergence and resurgence of infectious diseases and the problem of drug resistance along with the mounting costs of drug development programs and time gaps, it is only prudent to adopt and integrate computational techniques and programs in drug discovery pipelines to expedite the progress by turning the scale in our favor by cutting down costs of such ventures by shortening the drug discovery cycle and reducing efforts, manpower and time duration. Computational approaches have now become an integral part in storage, management, comparative analysis and in obtaining in-depth knowledge of disease due to their versatility. Computer aided drug design, genomics and proteomics, metabolomics, interactomics play a crucial role in mining hidden molecular information, pattern recognition and finally interpretation of biological significance. Computational chemistry is being widely used at different stages of drug design and production like target identification, target validation, lead identification and lead optimization in the pharmaceutical industry and has emerged as powerful tools complementing traditional chemical screening methodology. A synergistic relation between information technology and routine experimental approaches is required to handle and process voluminous and diverse datasets generated through genomics and high throughput screening methods and increasing the reliability of the outcomes. Incorporation of techniques based on artificial intelligence and use of large scale distributed computing for screening have provided a much needed impetus to drug discovery programs. Considering the array of disciplines and sub-disciplines involved with computational approaches and vast number of diseases we are dealing with, the topic requires series of issues to present the recent advancement and understanding on the subject. Our aim as editors is to bring forth informative articles that highlight the ongoing research in the computational front with respect to various diseases. We received enormous response and witnessed enthusiasm from the researchers to contribute in this series of issues. After successful completion of Part-I (Volume 18, Number 13), here we present the Part II (Volume 18, Number 31) with some selected articles summarizing interesting application of the implementation of computational approaches. The article by Salam et al. focuses on computational structural development and potential inhibitor targeting B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL), which are important targets for lymphoma [1]. Kaur and coworkers reviewed the structural insights required for the inhibition of HIV1 integrase [2]. Novel computational analyses for screening Cryptococcus species have been thoroughly outlined by Manjunath and Skariyachan [3]. Bashir and coworkers presented a general and overall perspective on the modern theoretical and computational aspects with respect to human diseases [4]. Kalra and coworkers highlighted the influence of physicochemical properties of functional groups such as ethers and esters at the 10th position of artemisinin derivatives in optimizing the anti-malarial activity [5]. Tiwari and coworkers reported Acetate kinase (AcK) as a broad-spectrum novel target in Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli [6]. Our sincere thanks are due to Dr. Allen B. Reitz, the Editor-in-Chief of Current Topics in Medicinal Chemistry for providing us this opportunity of bringing forth this special issue. It has been a great team effort. We would like to express our sincere thanks to Ms. Ambreen Irshad, Associate Editor and Maria Khan, Editorial Manager. We are thankful to the Editorial staff for their great support at every step of this issue. We are sincerely grateful to the authors for their contribution and patience during the review process. Contribution of the renowned reviewers deserves special mention; we acknowledge their support and efforts in scrutinizing manuscripts and providing valuable comments and suggestions for improving the quality of manuscripts. We believe that this special issue will be interesting for the readers of the journal.

Development of novel anti-cancer drugs is one of the most important theme in cancer research. Natural products and synthetic compounds have been searched extensively to cure different kinds of cancers and still search is on for finding novel compounds. Great effort has been done to find the target of anti-cancer drugs. Further target specific compound is being developed to cure cancer. Correlation between structure and function is one of the important aspects for success of anti-cancer compounds. In recent years strategic drug development program against the cancer has been initiated including high throughput screening of compound using bioinformatics, various cell lines, patient-derived tumor xenografts and drug delivery system. The purpose of this special thematic issue is to summarize the use of ongoing strategy for anti-cancer drug discovery and their valuable contribution for the expansion in the field of medicinal chemistry.

Microbial Bioinformatics is a rapidly evolving field of study that not only encompasses health and food science areas, but also presents new opportunities for advancement and innovation in engineering, manufacturing, and industrial process improvements [1]. As new sequencing methods become more cost effective and mobile, obtaining data for analysis is much less the obstacle than it once was [2-4]. The current resistance to widespread comprehensive data inclusion and diverse applied implementation of findings is the storage and computing power to analyze and organize raw data into usable and accessible formats. These hurdles will continue to be diminished with the improvement and application of new and more sophisticated algorithms as the artificial intelligence and cloud computing eases the current technological infrastructure burdens [5, 6]. The influx of omics data readily available for further analysis should be complemented by advancements in the structural modeling in order to ensure the structure-function relationships derived are sound. The complementary effect of greater sequence and structural refinement inputs serve to aid predictive elements as well as engineering of biomolecules, small molecule products, and in silico systems with medicinal or industrial purposes. Primary sequences dictate later modifications and structure [7]. To properly assess activity and function, the inclusive treatment of sequence, predicted modifications and corresponding structure, as well as the corresponding activities of such products in a systems perspective is imperative (Computational systems biology). Microbial systems have proven to be an invaluable simplistic model in systems biology, however when discussing medical microbiology in the context of antimicrobial design microbial system inputs are not easily directly transferable to human systems. This aspect may prove to be an advantage in development of antimicrobials that capitalize on these systematic differences in response to external perturbation (A network property necessary for concentration robustness.) Longevity, spectrum of coverage, and reduced toxicity of an antimicrobial treatment prove to be the difference between a theoretically good drug candidate, a later phase failure, and a true blockbuster global health improvement dictating medication. Precision medicine and pharmacogenomics is becoming more mainstream, as are more diverse and comprehensive microbial diagnostics becoming more affordable and accessible. The combination of systems analysis, structure-function relationships of small molecule drug candidates, and experimental findings from high-throughput screening and structural molecular dynamics validation methods provide improved stepping stones for drug discovery and development with expanded success limiting toxicity and maximizing the therapeutic effect [8, 9]. The complementation of experimental and computational sciences is ever apparent. As technological advancements in the areas of sequencing, data storage and acquisition, structural determinations, and systems biology arise, it is ever important that information is integrated and otherwise built upon for future studies to maximize available resources [10]. Funding, allocation of researchers’ time, and laboratory and computational resources need to be taken into account in order to maximize benefit while limiting redundancies that contribute to the lag between major findings in academia and their clinical implementation internationally. The academia to clinical availability factor of medicinally relevant small molecules will continue to improve, as will continually decreasing costs as more successful, promising leads are distinguished from less favorable leads earlier on and with greater ease in the drug discovery process [10, 11]. Distinguishing the winners from the losers earlier on in the drug discovery game will continue to contribute to less irrecoverable costs and less overall risk endured by drug manufactures in order to bring a new drug to market in an attempt to stay ahead of ever evolving microbial species presenting threats to human health globally, (Drug Delivery: Principles and Applications). 2. EXPLORING THE BIOLOGY AND STRUCTURAL ARCHITECTURE OF SORTASE ROLE ON BIOFILM FORMATION IN GRAM POSITIVE PATHOGENS Sortase enzymes are considered to be a powerful taught in all gram positive bacteria as it facilitates several functions including adhesions, internalins, blood clotting, immune evasion factors and transporters for nutrients across the microbial cell wall envelope. Due to its receptor availability, it is so called as universal drug target for gram positive pathogens. In present review Chandra Bose Selvaraj et al. they firmly explained a role of sortase in the virulence of pathogens and were focused on determining the role of Sortase enzymes' involvement in anti-infective studies and also, on the mechanisms of surface protein anchoring to the cell wall envelope by sortases, and highlight how it plays a strong role as drug target. Now it is considered as a promising target for the development of new anti-infective drugs that aim to interfere with important Gram-positive virulence mechanisms, evasion of host defenses, and biofilm formation. Many inhibitors of sortase have been identified using high-throughput or in silico screening of compound libraries, and also have proved useful tools for probing the action model of the enzyme, several are also promising postulant for the development into potent inhibitors [15, 16]. These research advances have greatly contributed to our knowledge of sortase cell wall anchoring, providing a platform for therapeutic targeting and further study in industrial applications. 3. ANTIFUNGAL ACTIVITY, MODE OF ACTION, DOCKING PREDICTION AND ANTI-BIOFILM EFFECTS OF (+)-β- PINENE ENANTIOMERS AGAINST CANDIDA SPP. Candidiasis is a most common fungal infection caused by yeasts that belong to the genus Candida. The antimicrobial activities of the isomers and enantiomers of pinene were evaluated against bacterial and fungal cells. In present study Ana Cláudia de Macêdo Andrade et al. exfoliated an example by using biochemistry and in silco approaches through molecular docking simulation and the effect on the biofilm reduction altogether to summarize, the mechanism of (+)-β-pinene most likely in interfering with the cell wall; maintain molecular interaction with Delta-14-sterol reductase and, to a lesser extent, with 1, 3-β-glucan synthase; is effective in the reduction of inhibition of the Candida biofilm [12-13]. (+)-β-pinene antifungal activity for effective to address candidiasis. Further, toxicological bioassays and phase I and II clinical trials are now needed to investigate the promising antifungal activity of the (+)-β- pinene as a potential candidate in the treatment of candidiasis which would be an innovative approach. 4. ANTIFUNGAL AND ANTIMICROBIAL PROPERTIES OF A PURIFIED PROTEASE INHIBITOR FROM MACROTYLOMA UNIFLORUM SEEDS Plant protease inhibitors (PPIs) are generally small proteins which play key roles in regulation of endogenous proteases and may exhibit antifeedant, antimicrobial, antifungal, antitumor and cytokine inducing activities. Macrotyloma uniflorum is an unexploited legume, which is rich in nutrients and promising therapeutic prospects. Manju Mohan et al. in the current study revealed the presence of a serine protease at active site. Future studies in this direction have to be performed to completely elucidate the characteristic features of Serine type protease inhibitor seed coat. The presence of protease inhibitor may be the cause for difficulty in human digestion and it’s role in processing antifungal and antimicrobial properties which can be used effectively for its application as a potential sea food preservative. An economical method to nullify the protease inhibitory activity which will increase the availability of a good protein source at a cheaper cost, thereby, making it a much needed protein source to meet the middle and lower class necessities [14]. 5. ANTI-HYERGLYCEMIC PROPERTIES OF A PURIFIED PROTEASE INHIBITOR FROM MACROTYLOMA UNIFLORUM SEEDS Hyperglycemia associated with diabetes mellitus is a major concern, which affects people with both type 1 and type 2 diabetes and be controlled by diet management, exercise, anti- hypoglycemic agents, and insulin therapy. Manju Mohan et al. in these current study evaluates anti-hyperglycemic activity of proteolytic enzymes purification which play central role in the biochemical mechanism of germination and is intricately involved in many aspects of plant physiology and development [17]. The inhibitory effect of purified protease on trypsin activity was characterized by enzyme kinetic study.To better understand the mechanism of protein mobilization, undertaken the task of purifying and characterizing proteases, which occur transiently. The overall study revealed that MUPI is an insulin sensitizer, and can be considered as a potent bioactive compound for diabetes. This innovative and challenging research will open up new avenues which constitute an effective anti-hyperglycemic protein which may find application in treatment of diabetes without evident toxic effects [18]. 6. STRUCTURE-BASED VIRTUAL SCREENING FOR THE IDENTIFICATION OF HIGH AFFINITY SMALL MOLECULE TOWARDS STAT3 FOR THE CLINICAL TREATMENT OF OSTEOSARCOMA Signal transducer and activator of transcription 3 [STAT 3] plays major role in cell signalling pathways, but over expression of this protein leads to osteosarcoma. STAT 3 is a latent cytoplasmic transcription factor which promote oncogenesis. STAT3 appears to be an important mediator of chemo resistance in osteosarcoma. Ravina et al. in the present study focus on decreasing the over expression of STAT3 protein by down regulating the pathway using chemical inhibitor to suppress STAT3 activity. Initial approach is made via in silico method based on docking studies and pharmacophore profiling to identify best pre-established compound [19-27]. Moreover a compound Sorafenib found to be best established drug with effective affinity towards the targeted protein. Interestingly, on further virtual screening investigation the total energy of virtual screened compound Pubchem CID-44815014 is better than the entire set of pre-established inhibitors with preferable affinity and inhibitory action. The study foresee Sorafenib and 44815014 are structurally cognate. Howbeit Sorafenib is efficient inhibitor, but novel compound 44815014 with great affinity towards STAT3 can be emerge as an important drug in treatment of disease the future ahead. Although, this research will open up new horizons to deliberate further utilization in in vivo and in vitro analysis. This research will contribute in determining the most effective chemical prospective to fight against osteosarcoma. 7. STRUCTURE-BASED VIRTUAL SCREENING APPROACH FOR THE IDENTIFICATION OF POTENTIAL ANTICANCER COMPOUNDS TARGETING CD20 FOR THE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) CD20 is a hydrophobic phosphoprotein commence on the surface of the human B lymphocyte cells, and play an essential role in the proliferation and differentiation of b-cells giving rise to humeral immune response, emerged as a tantalizing therapeutic option for the treatment of CLL. Kritika et al. in her study emphasis on determining drug which target chronic lymphocytic Leukemia (CLL) by constrain the activity of CD-20.Author rationalize the interaction of the CD20 with its pre-established inhibitors for CD-20 and to render the new compound having high binding consonance against the target protein. By virtue of Insilco approaches which includes depiction of targeted protein structure and validation by Ramachandran Plot [27-30]. Further docking studies carried out in addition with pharmacophore and ADMET analysis for toxicity [31-32]. Withal, conspicuous from the docking studies of pre-established and virtual screening [33-35] compound for CD-20 resulted in among all compounds top side with PubChem Id 36462 found to have good affinity among all pre-established compound for desired protein receptor CD-20, whereas on compelling this study virtual screened compound with PubChem CID-11753896 is inimitable for pharmacokinetics and it is preferable to pharmacological profile to prevent CLL cancer. This innovative and challenging research will open up new avenues which constitute an effective protein CD-20 which may find application in treatment of Chronic Lymphomatic Leukemia without evident toxic effects.

Epigenetics is the heritable change in gene function that does not involve changes in the DNA sequence. To date, several types of epigenetic changes have been characterized, including methylation, hydroxymethylation, acetylation, phosphorylation, ubiquitination, neddylation and so on. Most of these modifications can be read, written and erased on DNA, RNA and histone by specific modifiers. With the biological investigations of these modifiers, some of them are identified as promoters in the process of various diseases, such as cancer, cardiovascular disease and virus infection. Hence, targeting epigenetic modifiers has been considered as a promising strategy for disease treatment. To date, several epigenetic targeted drugs have entered clinic trials, or are currently being used in clinic, including a DNA methyltransferase inhibitor, bromo domain reader inhibitor, and histone acetylase or deacetylase inhibitor, histone methyltransferase or demethylase inhibitor, deubiquitinase inhibitor and neddylation inhibitor. Most of these drugs are applied in leukemia, lymphoma therapy, or are combined with other drugs for the treatment of solid tumor. This issue provides the up-to-date summary on some epigenetic targets and the development for related inhibitors for cancer therapy. The first review by Prof. Zigang Li and co-authors comprehensively summarized the biological roles of epigenetic targets and related inhibitors developed for cancer therapy. The second review by Prof. Weisheng Feng et al., comprehensively summarized the recent advances on the development of inhibitors targeting epigenetic targets, particularly those in clinical trials, and also gave their perspectives on the specificity, limitations and drug combination. The third review by Dr. Fanghui Lu et al., discussed HDAC inhibitors regarding their functional mechanism, the anti-tumor effects and potential clinical applications. The fourth review by Prof. Hao Fang et al., summarized recent advances on the structure and functions of HDAC6, and selective HDAC6 inhibitors. The last review by Prof. Feng Liu et al., summarized an array of nucleoside and non-nucleoside inhibitors of DNMTs, as well as their biological activities. I am grateful to all the researchers that contributed to this special issue and the referees for their insightful comments.

The important steps involved in the process of drug discovery are lead identification, lead optimizations, pre-clinical lead development, and clinical lead development. The contribution of computational design methods to lead identification and optimizations is no longer a matter of dispute. Exploitation of computational tools has not only reduced the cost but also the time in drug discovery. The last decade witnessed significant contributions of computational tools in many emerging areas of drug discovery viz. pharmacokinetics/pharmacodynamics, bioimaging, personalized medicines through system biology and drug repurposing. This special issue aims to cover the full spectrum of computational approaches relevant for drug discovery. Let us now discuss the content of this issue. The first review article is focused on the identification of drug binding sites and includes a comparison of three common approaches namely sequence-based methods, structure-based methods and probe-based Molecular Dynamics (MD) methods to identifying drug binding sites. Second review article is also related to hotspot/binding-site identification on protein surfaces, but this review article extensively talks about challenges and utilities of probe-based Molecular Dynamics (pMD) methods for the identification of small molecule binding sites. Third review article focus on current advances in the Fragment-based Drug Design (FBDD) approach. The subject of the following review article focusses on current status of application of ligand and structure-based approach targeting Anthrax virus. The last manuscript is a research article related to ligand and structure-based investigation of structural requirements for silent information regulator 1 [SIRT1] activation.

The important steps involved in the process of drug discovery are lead identification, lead optimization, pre-clinical lead development, and clinical lead development. The contribution of computational design methods to lead identification and optimization is no longer a matter of dispute. Exploitation of computational tools has not only reduced the cost but also the time in drug discovery. The last decade witnessed significant contributions of computational tools in many emerging areas of drug discovery viz. pharmacokinetics/pharmacodynamics, bioimaging, personalized medicines through system biology and drug repurposing. This special issue aims to cover the full spectrum of computational approaches relevant for drug discovery. Let us turn now to the content of this issue. The first review article talks about epidemics of viral diseases that adversely affects human population and the role of bioinformatic and immunoinformatic tools which can aid in vaccine design against these deadly diseases [1]. The second article is a review related to the recent advances and limitations of current pharmacokinetic modeling approaches and reveal some possible solutions to improve the applicability of in silico Caco-2 permeability models for absorption property profiling [2]. The subject of the following review article deals with the molecular modeling approaches for the prediction of pharmacokinetic properties [3]. Fourth review article offers us a vision on computational methods for binding mode and binding affinity prediction of peptide- MHC complexes [4]. The last manuscript is a research article related to lipid lowering, anti-oxidant and anti-hyperglycemic activity of oxopropanylindole hydrazone derivatives [5].

The interaction of with Medicinal Chemistry of new Enabling Technologies such as OMICS, Chem-Bioinformatics, etc., is expected to have a positive impact on the discovery of more effective and safe drugs. In this connection, Current Topics in Medicinal Chemistry journal is publishing a series of special issues entitled “New experimental and computational tools for drug discovery” to discuss all implications of this interaction in the broader sense. The series have published a total of four special issues up to date (1-4). The present issue is entitled: New Experimental and Computational Tools for Drug Discovery: Medicinal Chemistry, Personalized Medicine, Ethical, & Legal Issues. Part - V. In this sense, the issue presents a new collection of papers exploring the use of new methods of Medicinal Chemistry and Enabling Technologies in Drug Discovery. The issue also discusses the new aspects emerging from the interaction of Medicinal Chemistry with Personalized Medicine towards the development of safer personalized drugs in the future. In this connection, the issue also discusses not only chemical and technical methods but also ethical and legal concerns. The papers included in this part five can be summarized as follows: Clendenen & D’Alessandro pointed out that metabolomic analysis has made substantial contributions to the understanding of diverse pathological processes and has the potential to improve diagnosis and identify novel therapeutic targets. As early success in perinatal medicine, nutrition, chronic diseases, cancer and trauma demonstrates, metabolomics is approaching feasibility in terms of guiding improvement in population level diagnosis and treatment. This review covers key advancements in clinical metabolomics and applies a high throughput metabolomics method as a proof of principle to identify novel metabolites associated with remote ischemic preconditioning [1]. Malik et al. focused on the development of xanthine oxidase and monoamine oxidase inhibitors leading to important breakthroughs in the therapy of oxidative damage, hyperuricemia, gout, neurological, neuropsychiatric disorders and management of reperfusion injury. Drugs obtained from natural sources play an important role in treatment of various pathological disorders and act as lead compound for the discovery of new synthetic drug substances. In this review various pharmacological effects produced by inhibition of xanthine oxidase and monoamine oxidase through natural and synthetic flavanoids as well as anthraquinones are discussed in detail. In this review, all the in-vitro and other computational approaches are critically discussed which provided the clue about structure activity requirements for further precise modifications on the basic scaffold [2]. Duardo-Sánchez & De Miguel Beriain highlighted that Medicinal Chemistry and Personalized Medicine related to it, has received a great attention in recent years. Significant investment and remarkable researches surround the matter; however, not all those promising advances are reaching patients as quickly as they should. The absence of an adequate regulatory framework could be not helping. The complete and/or massive sequencing of individual genomes faces many ethical-legal challenges. Some of them are the access to Personalized Medicine; the treatment of a large volume of sensitive information and the use of tools produced by "big data" systems in clinical care or in predictive models. In addition, the legal protection of personal data related to health, the exercise of autonomy by patients, closely related to the regulation regarding clinical trials, are seriously involved. The purpose of this work is to review the regulations of the European Union, in this regard [3]. Sharma et al. pointed out that Renal Cell Carcinoma is a common type of renal cancer-causing deaths worldwide is characterized by sustained angiogenesis. Induction of VEGF genes occur due to hypoxic condition induced by tumour growth after a critical size in cancerous cell. Signal transduction networks originated by VEGFA/VEGFR2, (a notable ligand-receptor complex in the VEGF system) leads to major angiogenesis events ranging from endothelial cell proliferation, to new vessel formation. Furthermore, differential expression of VEGFVEGFR mRNA also found in different types of RCC. The aim of present study is to inhibit the VEGFR2 protein by the action of certain inhibitors and find the best one. A total of 23 potential inhibitors were searched and used to target the protein using the concept of molecular docking. The compound SCHEMBL469307 predicted have a high potential to inhibit the VGFR2 protein and can be backed for future studies in Renal Cell Carcinoma [4]. Ferreira et al. discussed that the increase in the prevalence of drug-resistant pathogens occurs at a time when the discovery and development of new antimicrobial agents occur slowly. In this context, the objective of this study was to investigate the antifungal activity of isoeugenol, a phenylpropanoid, by in vitro and in silico assays against Penicillium citrinum strains. For in silico analysis, the software PASS online, Molinspiration and Osíris were used. For the determination of Minimum Inhibitory Concentration (MIC) and Minimal Fungicide Concentration (MFC) of isoeugenol and voriconazole were carried out using the broth microdilution technique. PASS online has shown that isoeugenol has the opportunity to present antiseptic, antifungal, antibacterial, antimycobacterial activities. Molinspiration showed that the phytoconstituent has good potential for oral bioavailability. The MIC of isoeugenol varied between 256 and 32 μg/mL, MIC50 of 64 μg/mL and MIC90 was 128 μg/mL. After analysis, it was verified that the isoeugenol have bactericidal effect against the strains of P. citrinum [5].

Infectious diseases, such as endocarditis, chronic skin infections, middle ear infections and sinusitis are responsible for over 15 million deaths a year [1]. The high mortality rate is due to the widespread use of antibiotics in humans which cause increased resistance by bacterial strains. Microorganisms can induce antibiotic resistance by several mechanisms: hydrolysis or chemical modification of the antibiotic through the production of enzymes, alteration of the antibiotic target site, decrease in membrane permeability and/or increase active efflux of the antibiotic, and modification of the metabolic pathways to circumvent the antibiotic effect [2]. Moreover, bacteria in biofilms communicate by means of molecules, which activate genes responsible for the production of virulence factors (quorum sensing mechanisms). Current antibiotic therapy is generally effective against free-floating bacteria while it is often unproductive against pathogens forming biofilms because biofilm colonies can be up to 1000 times more resistant to conventional therapies [3]. Increasing resistance to antibacterial agents has augmented the need for the development of new drugs and drug delivery approaches to treat infections [4, 5]. Investigations concerning the development of novel strategies to overcome antibiotic resistance represent a great challenge for both the academic world and industry since bacterial infections represent a significant issue that includes several areas such as public health or food contamination [6, 7]. This issue highlights the chemical and pharmacological features of novel compounds to treat antibacterial infections and recent therapeutic approaches to overcome antibiotic resistance. The papers included in this special issue confirmed the importance of both well-known natural products with low molecular weight and antimicrobial peptides in the management of chronic and nosocomial infections. However, natural antimicrobial peptides and polyphenolics derivatives could suffer from chemical instability, photosensibility, and enzymatic degradation, which hamper their clinical use. Here, to overcome these limitations, medicinal chemistry approaches, such as chemical modifications, replacement of hydrolysis sensible groups or introduction of mimetics of natural amino acids, were analyzed and reported. Thus, this special issue collects latest advances in the field of antibacterial drug discovery and delivery such as the use of natural-based antibiofilm and antimicrobial peptides, naturally occurring prenyloxyphenylpropanoids, and polyphenolics as suitable clinical tools for the treatment of infections. The guest editor wishes to thank all the researchers that contributed to this special issue and the anonymous reviewers that, with their helpful and constructive suggestions and comments, improved the quality of the final version of the papers.

Infectious diseases cause remarkable human suffering, particularly in lowincome and middle-income countries. Infectious diseases are responsible for the vast economic burden globally. Efforts are going on to develop effective and safe therapeutics, however the rapid appearance of drug resistance in human pathogens, weaken the clinical worth of several current drugs. Therefore, the discovery of new anti-infectious molecules is highly demanded. This special issue comprises the up-to-date information on drug development for infectious diseases. The first contribution presents a review article focused on small molecules effective against liver and blood stage malarial infection was contributed by Dr. Singh and her co-workers from Miranda House, University of Delhi, India. This mini-review article covers library of chemical compounds effective against blood stage and liver stage malarial infections (i.e. dual stage activity). The second contribution was received from Prof. Samuel K. Kwofie and colleagues. This review focuses on the malarial aspartic proteases known as Plasmepsins (Plms) as novel drug targets and antimalarials targeting Plms. It further discusses inhibitors of hemoglobin-degrading plasmepsins Plm I, Plm II, Plm IV and histo-aspartic proteases (HAP), as well as HIV protease inhibitors of plasmepsins. The group led, Prof. Alo Nag and co-workers from University of Delhi South Campus, India contributed the next review article about ionophores as potent anti-malarials. This review presents an overview on the state-of-the-art of the relevant literature on ionophores, and provides insight into the mechanism and prospects of different classes of ionophores as promising antimalarial. Next, two articles were contributed by Prof. Ramesh Chandra and his team members from University of Delhi North Campus, India. The biological aspects of heme and its drug interactions with CYP450 have been reviewed. The last contribution is an research article that presents the designing of a novel indoline scaffold based antibacterial compound and pharmacological evaluation using chemoinformatics approaches. We are grateful to all the authors and referees for their valuable support to this special issue.

Research to discover new treatments for infectious disease has developed as a specialty during the past century. At global level, the burden of the infectious diseases is growing, particularly in low-income and middle-income countries, and susceptible populations. Infectious diseases trigger millions of deaths yearly. Widespread resistance of anti-infectious drugs remains a big threat, particularly when effective vaccines are not available for most of the infectious diseases. Subsequently, inventions of new therapeutics effective against infectious diseases are highly required. This special issue of Current Topics in Medicinal Chemistry contains the latest updates on molecular mechanisms, drug targets, drug development for infectious diseases in the form of high-quality articles from the various parts of the world. The first contribution presents a review article focused on antibiotics-peptide conjugates from the research group led by Dr. Rakesh K Tiwari, Chapman University, USA. This article deals with the advanced information on antibioticspeptide conjugates (APCs) extensively, as an approach to battle the threat of multi-drug resistance of bacterial pathogens. The adopted APC strategies and physicochemical properties that show how they can be used to increase the antibacterial efficacy are also discussed in detail. Next contribution deals with chemistry and biology of farnesol and its derivatives was prepared by Dr. Krishna Mohan Poluri from Indian Institute of Technology Roorkee, India. This interesting review discusses the biological roles, chemical-biochemical synthesis, metabolic engineering, and crucial biotechnological uses of farnesol based compounds. The third contribution entitled internet resources for drug discovery and design was received from Prof. Maria Grishina, South Ural State University, Russia. This comprehensive review highlights the possibilities of the internet resources for a study of a drug action at the most important stages. Also, a detailed assessment of advantages of the reviewed internet resources is presented. The fourth article entitled chemotherapeutic potential of monensin as an anti-microbial agent, presented by Dr. Vinoth Rajendran and co-workers deals with the therapeutic potential of monensin as a new broad spectrum anti-microbial agent that permits further investigations for clinical use. The last review article on apicoplast metabolism: parasite’s Achilles’ heel was contributed by Dr. Manmeet Rawat and co-workers from University of New Mexico, USA. This article describes the cardinal features of the methylerythritol phosphate (MEP) pathway enzymes and progress made towards the characterization of new inhibitors. MEP pathway is described as a repertoire of novel anti-malarials and antibacterial drug targets. The Guest editors are highly thankful to all the authors and referees for their valuable support to this special issue. Science and Engineering Research Board (SERB), Govt. of India is acknowledged for financial support (ECR/2015/000448). YK is grateful to the Department of Science and Technology (DST-SERB), Ministry of Science and Technology, India for financial support (YSS/2015/001966).

As it has already been stated [1, 2], basic neuroscience research is prevented from instrumentation into direct clinical application due to several methodological limitations, concerning extrapolation, penetrability and objectivity of the methods. In other terms a large part of neurobiological inquiry, including studies of neurochemical pathways, drug targets and mechanisms remain relatively discrepant from clinical utility. In this special issue there has been delivered strong evidence on the potential use of tetramethoxyluteholine and umbelliferone as treatment agents for neurodegenerative and neuropsychiatric disorders. However rather fundamental pharmaceutical perspective (drug synthesis) have been employed by Dhiman et al. [3] whilst Theoharides and Tsilioni [4] embrace more medical stance, with an emphasis on the drug target mechanisms in the cytokine-neuropeptide interactions. Further there has been achieved remarkable advance into in-vivo imaging of the underlying neurochemical processes in mental disorders which essentially provide insights beyond the aforementioned limitations of the traditionally adopted neuroscientific methods [2]. Those are in particular the methods of functional neuroimaging. Most promising progress in the application of magnetic resonance spectroscopy in the study of the metabolites involved in the pathogenesis of schizophrenia has been summarized by Dwyer et al. and for functional magnetic resonance imaging results with memory evaluation paradigms in bipolar disorders by Beshkov et al. [5]. This field of research is linked directly to the studies of novel molecular pathways implicated in various mental disorders [6, 7]. The bottom line message from our Special Issue is that the advances in applied neuroscience research bring together large scale experimental data sets spanning from neurochemical to neurophysiological and behavioral levels of explanation which should gradually aspire towards in vivo real time investigations of the biological substrate behind neurological and psychiatric disorders.

Design and development of new drugs is extremely expensive and resource-intensive process. During the past few decades, computer-aided drug designing/ discovery has played a major role in designing of new drugs in a cost-effective manner. Computer-aided drug designing utilizes concepts of structural/ chemical biology to efficiently identify and optimize lead compounds using computational tools and methods. Structure-based and ligand-based drug designing approaches are commonly employed for virtual screening/ identification of lead compounds or to improve the therapeutic potential of an existing lead compound. Homology modelling, virtual screening, quantitative structure-activity relationships (QSAR), density functional theory (DFT), molecular docking, molecular dynamics (MD) simulation and in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions as well as systems biology approach aids in the drug development process. This thematic issue is aimed to illustrate the pivotal role of computational techniques in unravelling the structure-function relationship to understand the molecular recognition events of target macromolecule with ligand leading to the design of improved lead candidate for the target receptor.

Applied neuroscience includes contributions and insights from neuro-biochemistry, molecular neurobiology, neuroimmunology, neuropharmacology and among others. The present topic embraces a complex multi-dimensional interface between basic neuroscience innovative study designs, novel molecular and bio-chemical markers and drug targets; advanced computational technologies and their implementation in clinical neuropsychiatry. It will address as well the interplay of complex neurobiological factors and psychosomatic disorders

Neglected Diseases are those that affect almost exclusively poor and powerless people living in rural parts of low-income countries [1]. They sometimes attract other labels, such as tropical diseases or poverty-related diseases. Neglected diseases include leishmaniasis (kalazar), onchocerciasis, Chagas disease, leprosy, tuberculosis, schistosomiasis, lymphatic filariasis, African trypanosomiasis (sleeping sickness), malaria and dengue [2]. Some are lifethreatening, while others result in high morbidity and severe disabilities [1, 3]. Currently some of these tropical infections have become a major global concern, due to serious sequelae; as Zika Virus and Ebola. Also, geographical distances between continents do not represent a barrier to infectious agents due to rapid transport. Infected human hosts can travel facilitating epidemics. The objective for this thematic issue was to report recent studies about different approaches in drug discovery, which comprises synthesis, semi-synthesis, the search for new targets, natural products, evaluation of biological activities, and/or theoretical approaches as structure-based approaches, SAR, QSAR, docking and several cheminformatics methods [2], for investigation and selection of new lead molecules. These efforts involve several studies to aid the drug discovery of new options for the treatment of neglected diseases. Dengue like any neglected tropical disease affects a large part of the world population. In this disease, the infection is caused by arboviruses transmitted by A. aegypti and A. albopictus mosquito, in which the most severe manifestation is known as dengue hemorrhagic fever. The infected person presents symptoms characteristic of fever and rash. Among the ways of fighting dengue by bioactives is the inhibition of NS2B-NS3 protease, inhibition of protein E, and inhibition of sclerotization of the vector cuticle. The cuticle is indispensable for the survival of the mosquito that can be compromised through the inhibition of arylalkylamine N-acetyltransferase (aaNAT). In our manuscript entitled Dengue Virus Inhibition Targets: A Review and Docking Study, in silico tests were performed as molecular docking, functional density analysis, molecular orbitals energies and of the interactions between the bioactive and the targets studied were analyzed. However, in addition to discussing the fight against dengue virus infection through different routes, some in silico results of 27 analogs of myricetin have been presented, which showed action on the cuticle sclerotization mechanism. Dengue Fever: A Worldwide Threat: An Overview of the Infection Process, Environmental Factors for Global Outbreak, Diagnostic Platforms, and Vaccine Developments by Hosseini et al, is a review article also focused on Dengue. The paper covers essential topics including an overview on neglected tropical diseases with specific emphasis on Dengue fever, mosquito's cycle of life and mechanism of infection, adaptive response, and different stages in Dengue immunopathogenesis. The current work is also dedicated to the thorough study of Dengue outbreak across the globe with a brief study of tropical and subtropical regions. Moreover, this review article demonstrates the correlation between the climatic factors and Dengue incidence. In the manuscript entitled, Discovery of Potent Inhibitors for the Inhibition of Dengue Envelope Protein: An In Silico Approach, Aarthy & Singh showed a study with the crystal structure of Dengue Envelope protein from the protein data bank optimized through Schrodinger. The structure based virtual screening based on the co-crystallised ligand has been carried out with the small molecule libraries and based on the docking score, interaction and energy values, best complexes were selected. The selected complexes were further taken forward for the conformational stability analysis through Molecular dynamics simulation. From the results it is evident that the compounds DB00179, Quercetin, Silymarin, Dapagliflozlin and Fisetin could be novel and potent candidates to inhibit the DENV envelope protein. Many of the tropical diseases are neglected by the researchers and medicinal companies due to lack of profit and other interests. The Drugs for Neglected Diseases Initiative (DNDi) was established to overcome the problems associated with these neglected diseases. According to a report published by the WHO, leprosy (Hansen's disease) is also a neglected infectious disease. The treatment used until now for leprosy is multi-drug treatment. The complete genome identification of Mycobacterium leprae makes the research easy to develop target specified drugs for leprosy. Rifampicin, identified as a potent drug, along with other drugs in uniform multi-drug treatment, has a significant effect when given to leprosy patients at initial stages. These are effective treatments but a specific drug for leprosy is still needed to be identified. The review of Aamir et al., Recent Advancement in the Diagnosis and Treatment of Leprosy, highlights the use of modern methods for the identification of leprosy at its earlier stages and the effective use of drugs alone as well as in combination. The manuscript of Hazra & Patra entitled Alleviating the Neglected Tropical Diseases: Recent Developments in Diagnostics and Detection discussed various novel research progresses/advancements made for qualitative and quantitative measurement of infectious load in some diseases like dengue, Chagas disease and leishmaniasis; though further improvements in the specificity and sensitivity front are still awaited. Strategies to combat the problem of antimicrobial drug resistance in the diagnosis of NTDs have also been put forward by various research groups and organizations. Moreover, the state-of-the-art “omics” approaches like metabolomics and metagenomics have also started to contribute constructively towards diagnosis and prevention of the NTDs. The aim of the study by Khan and co-workers, Formulation and Characterization of a Self-Emulsifying Drug Delivery system (SEDDS) of Curcumin for the Topical Application in Cutaneous and Mucocutaneous Leishmaniasis, was to develop a Self-Emulsifying Drug Delivery System (SEDDS) for the hydrophobic polyphenol pigment curcumin to enable it for its potential use in cutaneous and mucocutaneous leishmaniasis. The results demonstrated that the SEDDS formulations of curcumin have the potential to provide a promising tool for curcumin for its use through topical routes in the treatment of these diseases. Through virtual screening of a chemical library of 15,123 small molecules, analyzed by two programs, four potential inhibitors of phosphoglycerate mutase 1 from P. falciparum were found by Rios-Soto et al. The study was reported in the manuscript entitled Virtual Screening, Molecular Dynamics and ADME-Tox Tools for Finding Potential Inhibitors of Phosphoglycerate Mutase 1 from Plasmodium falciparum. Molecular dynamic analysis revealed that these molecules interact with residues important for enzyme catalysis and molecule ZINC04343691 provoked the highest structural changes. Physiochemical and toxicological profiles evaluation of these inhibitors with ADME-Tox method suggested that they can be considered as potential drugs. Furthermore, analysis of human PGAM-B suggested that these molecules could be selective for parasitic enzymes. In the manuscript of Thomas & Timson, entitled The Mechanism of Action of Praziquantel: Some Hypotheses; the authors discussed that there is a critical need to understand the biochemical pharmacology of the praziquantel in order to inform the discovery of the next generation of anthelmintic drugs. We, the Guest-Editors, would like to express our gratitude to the many authors who contributed to this special issue, reporting investigations of various aspects of Recent Advancement against Neglected Diseases.

Heterocyclic rings are considered the pillars of medicinal chemistry because they are merged into the molecular structure of most of the available therapeutic drugs in the market. Since the early days of medicinal chemistry, these rings were known to be important as structural feature responsible for the relationship between structure and biological activities. Taylor et al. [1] estimated that approximately six new ring systems are created per year and that some of these are incorporated into new drugs. According to the authors, 1,2,4 and 1,2,3-triazoles are among the top 100 most frequently used ring systems from small molecule drugs listed in the FDA orange book sorted by descending frequency. The sub-class of five-membered heterocycle [2-4] is widespread in nature [5] as well as in the therapeutic arsenal available to treat various diseases [6]. In addition, they have several representative drugs in the market for the treatment of disease as antifungal, anticancer, antiviral, β-lactamase inhibitor, anticonvulsant and antibiotic agents [7-11]. This special issue is based on seven manuscripts dealing with recent advances in the application of triazoles derivatives for treatment against infectious disease. Forezi et al. [12] reported a review covering synthetic methods that give access to other variations around the 1,2,3-triazole core. The systematic arrangement in this review explores the possibility of providing practical guidance to alternatives of this heterocycle. It has been divided into sections according to the types of starting materials and reactions. Heterocyclic rings having nitrogen atoms are the molecular fragments mostly used in drug design by using the tools of medicinal chemistry. Souza and colleagues [13] synthesized a series of naphthotriazolyl-4-oxoquinolines that exhibited potent in vitro antileishmanial activity involving at least two different mechanisms of action, making them promising lead compounds for the development of new therapeutic alternatives for leishmaniasis. Branco and coworkers [14] synthesized a series of naphthotriazolyl-4-oxoquinoline derivatives and tested their activity against a human breast cancer cell line. Among the compounds tested, a molecule was identified that killed the human breast cancer cell line MCF-7 with minimal effects on its healthy cell MCF10A. The selectivity observed against breast cancer cells make the molecule 12c a potential candidate as a novel anticancer drug. The antitumor mechanism involves the inhibition of glycolysis, diminished intracellular ATP levels, induction of ROS production and triggering of apoptosis. These effects are all selective for cancer cells, since the healthy cells are unaffected, and these effects can only be attributed to the whole molecule since different groups do not reproduce the effects. Reis and coworkers [15] prepared a series of symmetrical 1,4-disubstituted bis-1,2,3-triazoles by double Copper Catalyzed Azide-Alkyne Cycloaddition (CuAAC) from aliphatic bis-azides and a tetraethylene glycol bis-azide derivative. The novel compounds were evaluated in vitro for their cytotoxic activity against two human tumor cell lines: human breast adenocarcinoma (MDA-MB 231) and ovarian adenocarcinoma (TOV-21G). The results showed that some compounds exhibited a better selectivity index and cell viability comparable with the standard drug doxorubicin. These compounds induced apoptosis in both tested cell lines. The results suggest that these compounds may be promising prototypes for antitumor agents. Imbroisi-Filho and coworkers [16] tested several novel triazoles compounds for their putative anticancer activity and one molecule (DAN94) presented selective effects on cancer cells with minimal effects on non-cancer cells. The anticancer effect occurs through the disruption of mitochondrial potential which induced the production of ROS, triggering cell apoptosis. In parallel, cells are arrested on G1/G0 phase of the cell cycle, decreasing the ability of these cells to proliferate. On top of that, when administered to mice with xenograft tumors, DAN94 strongly reduced tumor growth with no toxic effect. These results suggested that DAN94 is a good candidate for anticancer drug due to its selective effects on cancer cells and should be tested in a pre-clinical trial. Costa et. al. [17] synthesized two series of the compounds containing 1,2,3-triazoles ring in their structures and biologically evaluated novel inhibitors of HIV Reverse Transcriptase (RT). The results of the biological evaluation showed that all compounds presented high RT inhibition values and lower or comparable inhibitory concentrations. Thus, new compounds could be considered lead compounds for the development of new antiretroviral compounds. Lal and coworkers [18] synthetized sixteen new hybrids and were tested in vitro for their antimicrobial activity. Some of the tested compounds exhibited promising antimicrobial activity and could be utilized for the development of the new and more potent antimicrobial drugs. All these publications confirm the importance of triazoles scaffold in the search for new biologically active compounds.

The classical methods of diagnosis in both parasitology and mycology require microscopic visualization as well as the identification of the microorganisms using their morphological characteristics. In addition in the case of fungi, it is necessary to use culture-based methods. However, these methods are tedious and usually not very sensitive and require trained personnel to perform them. Tools for the diagnosis and monitoring of the disease remains a challenge, since a diagnosis is misleading, erroneous or too slow, hinder effective treatments. As a result, new and low-cost assays are required to help physicians to establish an accurate and definitive diagnosis and to modify the strategies to control these infectious diseases. Alternatively, indirect methods have been developed, such as serology-based assays and more recently molecular- based assays. In this respect, this CTMC thematic issue includes extensive reviews of updated diagnostic methods. Recently, molecular techniques based on the amplification of nucleic acids have allowed the development of sensitive, specific and rapid diagnostic methods, however their high price and the requirement of infrastructures make difficult to apply them in low-resource countries. Dea-Ayuela et al. have analysed the main advances in the development of a molecular technique called Loop-Mediated Isothermal Amplification (LAMP) assay for the diagnosis of malaria, leishmaniasis and Chagas' disease as well as the feasibility of their implementation in developing countries and its use as point-of-care diagnostic tests [1]. Candida is a fungus that is present in the skin, mouth or intestine of healthy individuals whose growth is controlled primarily by the immune system. However, in certain circumstances, such as immunosuppression, the infection spreads to different organs causing an invasive candidiasis. Pitarch et al. compiles an extensive review of the diagnostic methods applied in the most serious forms of candidiasis, the invasive one, since the rapidity in making the correct diagnosis is fundamental in the control of the infection and the prognosis of the disease [2].

Infectious diseases are caused by bacteria, viruses, fungi and parasites and are one of the leading causes of human morbidity and mortality, being also responsible for huge economic losses in the livestock industry. Among the control measurements of infectious diseases are the correct diagnosis and the adequate treatment of patients or/and asymptomatic carrier. Unlike other pathogenic microorganisms, parasites and fungi are eukaryotic organisms, so their cells are very similar to human/animals cells, making necesary to search and develop drugs without side effect or toxicity to the hosts cells. The fungal and parasitic infections have a wide global distribution, however the therapeutic arsenal available in the XXI century remains extremely reduced, this problem is aggravated by the appearance of resistance to conventional treatments. Due to the indifference of pharmaceutical industry, non-profit organizations, such as universities or research centers, are doing an exhaustive effort in the identification of compounds with antiparasitic and antifungal activity. There are different approaches in the search for new drugs, such as High-Throughput Screening Tests (HTS), which allow for the evaluation of thousands of different biological compounds through robotic systems, the identification of the mechanism of action and subsequent development of compounds with the same mechanism, or computer-aided design that includes structure-activity studies or virtual screening, among others. On the one hand, the complexity of the host-parasite system makes that compounds with good activity in in silico and in vitro models do not correlate with good efficacy in vivo, either because they do not reach the parasite per se (many parasites are intracellular or are anatomically isolated) or because the parasite has different forms with different responses to the compound. Since these pathogens have accompanied mankind since many years and hence, there are numerous ethno-pharmacological and ethno-botanical data that support the use of different plants in the treatment of the infections produce by parasites and fungi. Some of them are collected in traditional Chinese medicine, Ayurvedic or in the traditions of various indigenous groups from different parts of the world. Due to the difficulty of accessing conventional drugs in many developing countries, WHO has included among health strategies the incorporation of traditional medicine (complementary and alternative) to health systems, as long as there are clinical investigations that guarantee its safety and efficacy. This CTMC thematic issue includes extensive reviews related to the natural, conventional and advanced pharmacological treatments of various fungal and parasitic infections. Passero et al., reviewed several studies to understand how active products obtained from plants can be used in the treatment of leishmaniosis, with special emphasis on those from Brazil. Vivancos et al., make an extensive review about the treatment of Giardia intestinalis, from conventional pharmacological treatments to the use of medicinal plants, probiotics and new formulations with the aim to reduce the appearance of resistance and toxicity. Several parasites are responsible for diseases in livestock and involve large economic losses. Sanchez-Sanchez et al., examine the different measures applied in the control of Toxoplasma and Neospora, responsible for abortions in livestock with special emphasis on chemotherapeutical guidelines taking into account the different stages of the parasite and the safety for the final consumer. Candida is a part of our habitual microbiota, however in certain circumstances it can behave like an opportunistic pathogen, generating from skin and mucous infections to serious invasive forms. González-Burgos & Gómez-Serranillos analyze clinical evidence on the effectiveness of natural products in the vulvovaginal candidiasis, including essential oils, honey and yogurt or plant extracts. Finally, Taborda et al., focuses on two of the most important systemic mycoses, paracoccidioidomycosis and histoplasmosis, and their major characteristics in epidemiology, clinical aspects, treatment and laboratory diagnosis.

To rush to edit a special issue requires a lot of energy, motivation and constancy. When we started to consider the idea, it seemed a quite complicated challenge because our day to day struggle, as well as the authors and collaborators, were already strenuous. However, after many talks and discussions we decided to start this project. Various factors acted as detonators of our determination. We believe that the modern University cannot be just a factory of employees, but of people committed to the community and to the culture. In this particular case, we speak of the scientific culture but with the widest possible sense, making it a support of our humanity itself. The implementation of these foundations configures the hegemony of certain relational and understanding principles, of a vision of science, the life and the world. Beyond the particular positions and the over-meant local conditions that envelop all that remains within their reach, the moment we currently live allows us to identify the planetary expansion of scientific thoughts, risky theoretical and practical approaches. They all acquire countless forms allowing the apparent difference to be valued and signified. Unraveling this avalanche of progress and events is not only a necessity for knowledge, but a social urgency in the face of global conditions. As new generations are integrated into science, it is imperative to convey knowledge to them. This gives a community wherein the other is heard, developing strong links between the old and young generations. It is now time to analyze the two points of maximum relevance in these special numbers: the focus of the publication and the target audience. With regard to the first, we have focused on works that sketch modern settings and particular allusions to topics that under our point of view we consider the most relevant. At this time, we can guarantee that the chosen works include some of the most avant-garde proposals and initiatives, in tune and synchrony with the spirit of the publication. These articles are contemporary reflections that reread the present and open horizons beyond rigid and inflexible schemes. But not without giving up scientific rigor and, above all, the interconnection between different branches of knowledge. The second point to take into account focuses on the potential audience. When a publication with several authors and points of view assumes an expositive function it is difficult to specify the limits of that audience without having the idea of each one of the contributors. Such standpoint offers different approaches, which do not stop evolving, just like the audience itself. As an example, communication channels, audience profile and continuos increase of the multidisciplinarity make it difficult to homogenize the perspective. That is why we have tried to guarantee a wide outlook of the subject, seeking to ensure the authors to introduce their subjects with a general and accessible style and increasing the complexity and depth of the study progressively. We thus guarantee the possibility that each reader will extract the appropriate information and adjusted to their specific needs. Let us turn now to the content of this issue. The first manuscript has been reserved for both of us, as editors. Our goal was to introduce the general subject and make a critical view of the state of the art. We know that the biopolymers are the fundamental basis of chemical medicine and try to encompass everything is impossible. Therefore, we decided to organize the work focusing on their interactions with different types of materials (organic and inorganic) and the most technologies used: bulk and microfluidics. The next article is a review related to the development of new classes of antibacterial drugs. This review is focused on the worldwide problem provenient from bacterial resistance that will generate 10 millions deaths per year in 2050. The authors present different topics the reason for the decreased development of antibacterial agents, current strategies in antibacterial drug development, new mechanisms of action, and clinical development. The third article focuses on a computational vision on physicochemcial properties of biopolymer-material complexes. It offers a wide and contemporary vision of computational techniques with the most impact on biomedicine, more specifically: a combination of machine learning techniques and perturbation theories. The subject of the following article deals with the mechanical properties of biomaterials. Areas focused on tissue engineering or bone regeneration are not understood without the knowledge of the mechanical properties of the constituents. In this study the authors introduce us in the field of rheology by studying and analyzing some of the most important bioceramics in medicine. We shall turn to the next manuscript, a review that is focused on the most relevant colloidal drug delivery systems describing the effects of surface charge, hydrophobicity on bilogical response and the different strategies to modify the surface of organic, inorganic and biological materials. The sixth chapter offers us a vision on the structure and hierarchy of collagen not only from a biological perspective but also explains its potential applications in medicine. The seventh article is focused on the function of allyl isocyanate (AITC)-loaded Polylactic-co-Glycolic Acid (PLGA) as anticancer. The targeting ability was tested in HeLa cells demonstrating more effective anticancer properties compared with free AITC and their citoxicity was even more pronounced when a anti-EGFR antibody was covalently attached to the NPs surface. Additinally, the importance of this manuscript is that the proposed system (antibody-functinalized AITC-loaded PLGA NPs) was especifically located in squamous carcinoma A431 cells in comparison with non-functionalized NPs that were distributed randomly. The last manuscript is a research article related to two new materials for the encapsulation of bioactive compounds as carvacol: Pectin (PEC) and Aloe-gel (AG). The authors characterize this PEC/AG film for different techniques demonstrating the optimal concentration to microencapsulate carvacol.

Aims & Scope: Burgeoning rise in different disease cases such as cancer, viral diseases including Dengue, Chikungunya, Zika, Ebola, Japanese encephalitis, etc., other tropical and neglected diseases, metabolic conditions such as diabetes and many other health conditions warrants the need of immediate investigations and end the human plight for ensuring a better tomorrow. Advances in scientific research have shown the impact in eradication and prevention of many diseases conditions such as polio. Interplay of experimental and theoretical approaches have come a long way in proving their effectiveness and worth in this regard. Earlier computational approaches were almost ignored by a large section of the scientific community. Last few decades have witnessed a drastic change in the existing beliefs and today theoretical techniques are not only supporting and supplementing experimental results but also guiding studies by providing valuable cues. Computational approaches pertaining to understanding complex biological system have come a long way during past few years rising from its infancy to blooming into a full-fledged science. Simple bioinformatics and chemo-informatics approaches are being frequently applied in the arena of system biology and are providing remarkable insights on unsolved and unanswered scientific questions so far

At present, with the continuous development of bioinformatics, computing technology has been successfully applied in all aspects of pharmacy and medicine. Among them, the identification of drug-target interactions, synergistic drug combinations and drug repositioning based on heterogeneous biological data and powerful computational models are important topics in computational biology. Research on these important issues is not only for a better understanding of the various interactions and biological processes, but also for the development of new drugs and the improvement of human drugs. Previously, drug research faced an important problem that was difficult to solve. Since multiple targets usually involve the same disease, following a single disease, a single target, a single drug paradigm does not have the desired effect on accelerating drug discovery. Recently, in order to improve drug efficacy and overcome problems before drug resistance, the development of multi-target drugs has received much attention. It is well known that despite drug-target interactions, experimental assays for synergistic drug combinations and drug repositioning are very valuable and have made significant contributions to drug research, but the technical challenges make these experiments time consuming, expensive and limited to small scale studies. Surprisingly, computational methods can provide new predictions for experimental scientists and narrow the scope of candidates to accelerate drug discovery. Therefore, the development of a powerful method for the effective detection of potential drug-target interactions in a genome-wide manner, synergistic drug combinations and drug-disease associations is urgent. Using these computational models to obtain potential predictions with higher scores, and implementing biological experiments to verify, will greatly reduce human and material resources. The following pages of this issue are seven papers presenting current application of computational techniques in pharmacy and medicine, representing only a small portion of current research. The following is a brief description of these papers. In the opening paper of this issue, Muhammad et al. comprehensively presented the latest advances in drug target interaction identification methods and their use in drug multi-pharmacology [1]. In the second review, Ding et al. summarized the latest advances in computational methods for predicting effective drug combinations in a number of ways, including various datasets for discovering synergistic drug combinations, feature-based similarity measures and machine learning methods, as well as web-based methods that reveal synergistic drug combinations. In addition, the calculation method for predicting effective drug combinations was analyzed and predicted in this article [2]. Zhang et al. discussed current knowledge about ncRNA and network pharmacology-regulated genes involved in pulmonary arterial hypertension, as well as potential drug targets for pulmonary arterial hypertension [3]. Zhang et al. comprehensively reviewed the drug toxicity prediction studies based on machine learning in recent years, and compared the performance of the models proposed in these studies in terms of accuracy, sensitivity and specificity, providing the current state-of-the-art in this field and highlighting the issues in the current studies [4]. Wang et al. outlined the structure-based drug design used in drug discovery and highlighted its recent successes and major challenges of the current structure-based drug design approach [5]. Hao et al. summarized common methods for using protein-protein interaction networks to aid disease research and drug discovery, including network topology analysis, identification of new pathways, drug targets, and subnetwork biomarkers for disease [6]. Dong et al. discussed in detail the progress of parallel acceleration molecular docking software based on different common high performance computing platforms. Not only is the existing suitable program optimized and ported to the high performance computing platform, but many novel parallel algorithms are also designed and implemented. In addition, this article focuses on the techniques and methods used to parallelize docking software and recommended exemplar case studies [7]. We would like to express our sincere gratitude to all authors and reviewers for their contribution to this issue. We would also like to extend our appreciation to the Editor-in-Chief, Dr. Allen B. Reitz and the editorial staff of Current Topics in Medicinal Chemistry for their excellent support and providing us with the opportunity to pursue this hot topic issue.

Enabling technologies like Computational Chemistry, Bioinformatics, Combinatorial Chemistry, Metabolomics, Proteomics (OMICS in general), etc., are expected to speed up the discovery of more efficient and safer drugs in Medicinal Chemistry. Recently, this journal has launched a series of special issues focused on this topic. The title of this series of special issues is: New experimental and computational tools for drug discovery: From chemistry to biology. Four (1-4) special issues are currently available. In these issues, experts from around the world discuss the state-of-art and/or report new methodologies. The methodologies focus on organic synthesis of new lead compounds, the in silico screening of new lead compounds, computational discovery of drugs from natural compounds isolated from plants, the repurposing of known drugs, re-engineering of cost-effective medicines, nano-systems for drug release, etc. The present issue is entitled: New experimental and computational tools for drug discovery: From chemistry to biology. Part 4. Metabolomics, Pharmacokinetics, and Medicinal Chemistry. Part 4 is the continuation of the series and provides six papers focused on new technologies used in drug discovery, but this time with emphasis on Metabolomics, Pharmacokinetics, and Medicinal Chemistry. The papers included in Part 4 can be summarized as follows: Gross et al., [1] point out that metabolomics experiments generate a rich array of complex high-dimensional data. They suggest that this may, in part, account for past and more recent incomplete replications of previously specified biomarker panels, especially if not adequately considered. Herein, they identify common impediments challenging the analysis of raw, targeted Metabolomic abundance data and review methods that may remedy these issues, based on personal experiences and those of others. In doing so, they propose an analytical pipeline suitable for the pre-processing of data prior to downstream biomarker discovery. González-Domínguez et al., [2] present work focused on intervention and observational trials as complementary tools in Metabolomics. The authors provide a review of the literature regarding the application of metabolomics in assessing metabolic alterations with diabetes, diabetic insulin resistance, and provide an oral glucose tolerance test case study to demonstrate the complementarity of observational and interventional study designs. Kataria et al., [3] presented a work on the role of morin in Neurodegenerative Diseases (NDDs). NDDs are known to cause profound effects on families and patients, and a tremendous financial burden on the healthcare system of most populations worldwide. Morin, being a super antioxidant compound, may help prevent and mitigate such disorders by suppression of Reactive Oxygen Species (ROS) and through the inhibition of multiple additional targets. In this review, the authors discuss various neuropathological conditions and their specific target sites that may be relevant to morin’s neurobiological mechanisms. Bueso-Bordils et al., [4] focused on obtaining microbiological and pharmacokinetic predictive equations. They reviewed the state-of-art in the area and also reported a new study. Multi-Linear Regression (MLR) analysis was carried out in order to accurately predict physicochemical properties and biological activities on a group of antibacterial quinolones by means of a set of structural descriptors called topological indices. The aim of this work included developing prediction equations for such properties, after reviewing the relevant literature on antibacterial quinolones. De Sousa Eduardo et al., [5] focus on the requirement of research related to new antimicrobial agents, as increasing numbers of microorganisms expressing antibiotic-resistance are emerging. In this paper, the authors review the topic and also pro- De Sousa Eduardo et al., [5] focus on the requirement of research related to new antimicrobial agents, as increasing numbers of microorganisms expressing antibiotic-resistance are emerging. In this paper, the authors review the topic and also provide verification for the activity of a phytoconstituent against Escherichia coli strains ATCC 25922 and Staphylococcus aureus ATCC 25923. The authors recommend further investigations, utilizing different methodologies assessing whether (+) - α- pinene may provide an effective compound in future antimicrobial therapy. Srivastava et al., [6] focused on the inhibition of biofilm and virulence factors associated with Candida albicans by the partially purified secondary metabolites of Streptomyces chrestomyceticus strain ADP4. Despite several advancements in antifungal drug discovery, fungal diseases, such as Invasive Candidiasis (IC), remain associated with inordinately high rates of morbidity and mortality worldwide. In this paper, chemical profiling indicates that ADP4 secondary metabolites contained potentially beneficial alkaloids, flavonoids, polyphenols, terpenoids and triterpenes. The authors also report other experimental and computational findings.

Infectious diseases are still one of the main cause of mortality and morbidity worldwide. In addition, antimicrobial resistance is a well-recognized global threat; hence, necessitates the development of tough policies to control the spread of disease-causing microorganisms coupled with antimicrobial stewardship strategies and new therapies to reverse this process. In order to fight against microbial infections, we need new antimicrobials. Much effort has been infused by the scientific community in the past to the search of new and potential antimicrobials. Researchers have explored antimicrobials based on plants, microorganisms, and even synthesized new compounds. This issue deals with the important developments related to the topic of antimicrobials, especially, plant-based antimicrobials, β-lactamase inhibitors, new synthetic drugs, and also about the target based drug delivery system in case of chemotherapeutic agents. Singh et al. have discussed the importance of plant antimicrobials of the past decade (2007-2017). As plants are the major contributors of vast number of compounds, the plants have remained the indispensable source of medicine, and thus plant based antimicrobials are important to be considered. Most of these compounds are produced as secondary metabolites and their medicinal properties may be beneficial for the human being also. The synthetic chemistry has offered various molecules but most of these are directly or indirectly related to some plant source. In the current review, they have presented the plant-based antimicrobials reported between 2007 to 2017. Genera where most of the researchers have concentrated during this period includes, Thymus, Helichrysum, Quercus, Jatropha, Gnaphalium, Acalypha, and Lippia. Some other miscellaneous gene on which one or two reports are available include, Conocarpus, Chamaesyce, Bucida, Boehmesia, Pancratium, Artemisia, and Cinnamosma [1]. Wang et al. emphasized the development of β-lactamase inhibitors as potential antimicrobial agents. Horizontal transfer of the genes encoding metallo-β-lactamases (MBLs) among Gram-negative bacteria pathogens has led to the emergence of drugresistant pathogens, which now represent a major threat to the human health. It is urgent to develop new antibiotic agents to fight against antibiotic resistance. Metallo-β-lactamases (MBLs) are an important class of Zn(II)-dependent enzymes that can hydrolyze almost all β-lactams and render bacteria resistant to antibiotics in the clinic. To date, there are no clinically available MBL inhibitors although a large number of MBL inhibitors have been identified. In this review, they have highlighted the recent developments in small-molecule MBL inhibitors in the past decade [2]. Kaur et al. synthesized and characterized a new series of diazenyl chalcones by combining the azo and chalcone moiety together and evaluated them for antimicrobial and antioxidant potential. Some of the derivatives had shown high antimicrobial and antioxidant activity as compared to the standard drugs and hence presented new lead compounds for the development of novel antimicrobial agents [3]. Conventional chemotherapeutics lack the specificity and controllability, thus may annihilate healthy cells while attempting to annihilate cancerous ones. Newly developed nano-drug delivery systems have shown promise in delivering anti-tumor agents with enhanced stability, durability, and overall performance; especially when used along with targeting and triggering techniques. Ahmed et al. traced back the history of chemotherapy, addressing the main challenges that have encouraged medical researchers to seek a sanctuary in nanotechnological-based drug delivery systems that are grafted with appropriate targeting techniques and drug release mechanisms. A special focus will be paid towards acoustically triggered liposomes encapsulating doxorubicin [4]. As a whole, all these papers illustrate the versatility of this topic and highlight the importance of developing new prospection tools to advance the discovery of new compounds. I want to thank Bentham Science Publishers especially, the Editor in Chief Dr. Allen B. Reitz, who provided me the opportunity to contribute this thematic issue on such a topic and also all the editorial members for their continued support and cohesive interactions. I express my highest gratitude to all the contributing authors for their commitment, subject expertise, dedicated work, healthy coordination and support to me throughout the issue. I would also like to pay special thanks to all the reviewers for spending their valuable time on critical analysis of the manuscripts and providing valuable suggestions for further refining the manuscripts. At last, I am also thankful to all our readers.

Infection or colonization, contrary to what many people think, does not necessarily imply immediate damage to the host. From birth, beneficial microorganisms coexist and develop within us for a long time. However, when such organisms cause damage to the host body, an infectious disease with the associated symptoms and pathology is contracted. From a clinical point of view, a pathogen is any microorganism capable of developing as an infectious disease; where differences in pathogenicity depend on virulence. Infectious diseases caused by pathogenic microorganisms, such as bacteria, viruses, parasites or fungi can spread, from person to person, directly or indirectly and throughout a community. The studies united in this issue demonstrate the efforts of research to combat such infections and reduce the social cost of these diseases. Antimicrobial resistance is a major global concern. Strains of Tuberculosis (TB) resistant to rifampicin and other drugs challenge patient survival and public health. The World Health Organization (WHO) [1] has issued treatment guidelines for drug-resistant tuberculosis since 1997, and last updated these guidelines in 2016 based on the assessments of patient data in both published and unpublished studies. As the first choice for patients assailed by Multiple Drug Resistant Or Rifampicin Resistant (MDR/RR) strains, WHO recommends a standardized treatment regimen of from 9 to 12 months. Mycobacteria are characterized as slow-growing bacillus having a cell wall composed of highly lipophilic mycolic acids. The nature of this cell wall is of most importance to the development of new candidates for anti-tuberculosis (anti-TB) drugs. Mycobacterium tuberculosis is an intracellular pathogen highly adapted to its natural host: the human. Its cell wall, consisting mainly of mycolic acids, forms a hydrophobic barrier that confers resistance to both desiccation and discoloration by alcohol or acid. In our review, entitled Multi-Target Antitubercular Drugs, we reported the discovery of 3 classes of compounds that can simultaneously interact with more than one target of Mycobacterium tuberculosis. Increased incidences of Candida infection have augmented morbidity and mortality in the human population, particularly among severely immunocompromised patients and those having a long stay in hospitals (nosocomial infections). Many virulence factors and fitness attributes are reported to be associated with the pathogenicity of Candida sp [2]. It can cause infections ranging from easily treatable superficial type to life-threatening invasive infections. Additionally, it has the capability to infect humans of all age groups. Indeed, overutilization of broad-spectrum antibiotics has further complicated the scenario by leading to the emergence of less sensitive Candida strains, especially non-albicans. Despite our developed armamentarium, the diagnosis and treatment of human fungal infections remain a challenge. The review of Dr. Srivastava and co-workers entitled Emerging virulence, drug resistance and future anti-fungal drugs for Candida pathogens, focused on the prevalence of Candida spp. as human pathogens with emerging resistance to existing anti-fungal drugs. Furthermore, factors and mechanisms contributing to the pathogenicity of Candida spp. and the challenges being faced in combating the devastating infections associated with these pathogens have been discussed. Also, pros and cons of the current and future anti-mycotic drugs have been analyzed. Current study assesses the in-vitro antimicrobial activity of the crude extract of D. retusa (whole plant) and its derived fractions against clinically isolated human pathogenic bacteria and fungi [3]. In the manuscript Evaluation of In-Vitro Antimicrobial Potential of Daphne retusa Hemsl. against Human Pathogenic Bacteria and Fungi, Dr. Nawab et al. studied D. retusa as powder dried Extracted with methanol (E1). The study showed that D. retusa had a very good inhibitory action against different bacterial and fungal strains. All of the extracts were active almost against every microorganism used in the study. E2 has maximum percent inhibition against bacterial growth while E1 has maximum percent inhibition against fungal growth. Streptococcus pneumonia was the most susceptible bacteria while among fungi, Gongronella butleri showed the highest susceptibility. Onion (Allium cepa L.) and garlic (Allium sativum L.) extracts are traditionally used in many cultures as antimicrobial agents. Nonetheless, there is still a dearth of scientific validation pertaining to the antibacterial and possible antibiotic potentiating activity of these plants [4]. In the work Onion and garlic extracts potentiates the efficacy of conventional antibiotics against standard and clinical bacterial isolates of Dr. Mahomoodally and co-workers, decoction as traditionally used and methanol, ethanol, ethyl acetate, and acetone extracts of onion and garlic were evaluated for their antibacterial activity against 15 bacterial strains (6 ATCC strains and 9 clinical isolates) using the broth microdilution method to establish the minimum inhibitory concentration. The bacteriostatic and bactericidal actions were determined as compared to conventional antibiotics (streptomycin and chloramphenicol). Fractional Inhibitory Concentration (FIC) was determined to establish any synergistic interaction between the extracts and antibiotics using a modified checkerboard assay. The observed antibacterial activity might be justified due to the presence of high concentration of phenolic compounds in the extracts. This study has provided an opportunity to establish valuable baseline information on the antibiotic potentiating activity of onion and garlic, which can be further exploited for the treatment and/or management of infectious diseases. Some research has shown that Lippia pedunculosa Essential Oil (EOLP) has interesting biological activities. However, its low water solubility is the main challenge in achieving its therapeutic potential [5]. In this context, Cyclodextrins (CDs) have been widely used in order to overcome this problem due to their capability to improve the physicochemical properties of drugs. In this perspective, the main goal of the study of Dr. Menezes et al. entitled Physicochemical characterization and antinociceptive effect of β -cyclodextrin/Lippia pedunculosa essential oil in mice was to investigate how the improvement in the physicochemical properties of inclusion complexes (EOLP and β-CD) enhances the antinociceptive effect in mice. We, the Guest-Editors, would like to express our gratitude to the authors who contributed to this special issue, reporting investigations in various aspects of Perspectives on Infectious Diseases: Progress and Therapeutics.

The discovery that the members within a protein complex are not only found in close proximity but also talking to each other has expedited development of both experimental and computational techniques, which are used for studying protein-protein interactions (PPIs). The former provides information regarding the existence of the interaction and it also helps on the identification of the interaction interface. In spite of emerging roles of PPIs as novel drug targets for treatment of various crucial diseases over the past decade the field is still far from having a holistic understanding of the mechanism of interaction. Therefore, experimental techniques should guide and/or complement computational studies in order to develop efficient therapeutic molecules having higher affinity and lower side effects. In this special issue, we aim to summarize recent experimental and computational techniques used for studying PPIs as well as their possible application on selected biological problems of great significance in an effort to development of novel drugs that target PPIs. Among many others NF-kB, NSP1, MDXM, GPCRS, CD-40, BAFF-BAFF-L are some of the systems that have been revised.

Cyclic peptides and peptidomimetic molecules (modified peptides) play critical roles in natural processes, and can also be synthesized for use as research tools and therapeutics. Protein-Protein Interactions (PPIs) play central roles in regulating almost all biological processes across organisms and the central dogma of biology. Compared to small molecules and antibodies, peptides are advantageous for targeting PPIs because they maintain conformational flexibility, can be synthesized using relatively straightforward techniques and are generally less expensive. However, linear peptides are limited by poor stability and inefficient cell membrane permeability. On the other hand, cyclic peptides offer improved metabolic stability, bioavailability and selectivity compared to their linear counterparts; moreover, cyclic peptides are particularly useful for targeting PPIs because they maintain these enhanced drug-like properties without compromising bioavailability, as often occurs with linear peptides. Thus, the development of cyclic peptides and peptidomimetics is of great interest in medicinal chemistry, as evidenced by numerous investigational and approved cyclic peptide pharmaceutical compounds. This thematic issue is comprised of six strong papers authored by esteemed colleagues renowned for their work in the field of medicinal chemistry. The overarching topics covered include cyclic peptides in natural and therapeutic settings, the design of cyclic peptides, several approaches to synthesize cyclic peptides, and examples of cyclic peptides in biological systems. First, Rubin and Qvit present the first comprehensive review, analysis and critique of backbone-cyclized peptides, discussing their design, construction, development, and application. To address the construction of backbone-cyclized peptides, Rubin, Tal- Gan, Gilon, and Qvit subsequently provide a detailed guide for the conversion of protein active regions into peptidomimetic therapeutic leads – delineating the identification of PPI sites, the definition of bioactive pharmacophores and the use of backbone cyclization and cycloscan techniques to develop lead compounds. Next, Perez reviews additional approaches for design of peptidomimetics and discusses their core properties, while comparing and contrasting the medicinal chemistry and biophysical approaches for discovery and development. Testa, Papini, Chorev and Rovero extensively discuss approaches to synthesize cyclic peptides and peptidomimetics, including in depth analysis of the chemistries required to perform ring closing metathesis, lactamization, copper-catalyzed azide alkyne cycloaddition, and other cyclization reactions. Following this, Hillman, Nadraws and Bertucci delve into stapled peptides and focus on recent advances in their use for targeting PPIs therapeutically. Lastly, Mull, Harrington, Sanchez, and Tal-Gan present examples of cyclic peptides in biological systems through an analysis of cyclic peptide scaffolds in signal transduction pathways across a spectrum of prokaryotic and eukaryotic organisms as models for the discovery of novel and broadly applicable therapeutic lead compounds. It was an honor to compile this timely issue. Thanks to the journal for providing the opportunity for our colleagues and us to share our perspectives. We hope the readers find this material engaging and useful, and that it will inspire further inquiry and applied works.

Cancer metabolism is an emerging area of research that offers an opportunity to target specific metabolic vulnerabilities of cancer cells. Cancer cells undergo oncogene-mediated metabolic reprogramming in order to meet their energy demands. Cancer cells adapt to their microenvironment and rewire their metabolism to rely heavily on anaerobic glycolysis, a phenomenon known as the ’Warburg effect’. In addition, cancer cells get addicted to glutamine and also up regulate fatty acid synthesis to support their survival and rapid proliferation. Recently, there has been a resurgence of interest in targeting carbohydrate, amino acid, and fatty acid metabolic pathways for treatment of cancer and overcoming drug resistance in chemotherapy. Other emerging concepts include targeting mitochondrial metabolism for the treatment of cancer. The overarching theme of this issue is to highlight the current application, advances, and emerging concepts in the field of cancer metabolism and discuss the prospects of metabolic inhibitors as next generation cancer therapeutics. The issue will also emphasize medicinal chemistry efforts aimed at developing small molecule inhibitors targeting aberrant cancer metabolism.

No Text Found

The term "alternative" is employed to describe the test method in association with the principles of the 3Rs - Replacement, Reduction and Refinement. In accordance with this principle, an alternative method can be used to replace animal testing, reduce the quantity of animals required for each assay, or refine an animal testing method to minimize pain and suffering. There are different platforms available to create alternative methods including in vitro models and computer-based systems. A few elements may be considered in terms of safety when it comes to the development of a new drug or biomaterial. First it is important to identify the chemical identity and the composition, as well as chemical structure, impurities and functional groups, followed by the determination of the physical chemical properties. As a next step, the kinetics aspects, e.g. absorption, distribution, metabolism and excretion should be evaluated. The mode and /or mechanism of action or adverse outcome pathways as well as the chemical and biological interaction must be determined. Finally, the responses found in alternative assays can lead to a proper safety assessment for drugs and biomaterials without the need for animal experimentation. Within this context, this thematic issue focused on alternative assays applied to replace animal testing in order to assess the safety and biological activity of currently available and novel drugs and biomedical devices. The manuscript entitled "Epithelial organotypic cultures: a viable method to address the mechanisms of carcinogenesis by epitheliotropic viruses" describes the mechanism of carcinogenesis, a topic that was initially researched mainly in animal models. In another context, some alternative methods have also been employed in biomaterials, as the authors of “Current Methods Applied to Biomaterials – Characterization Approaches, Safety Assessment and Biological International Standards” extensively described. This review shows that using alternative tests for biomaterials has almost replaced animal tests, following an actual tendency. Finally, the last two manuscripts, “Validation cytotoxicity assay for lipophilic substances” and “Alternative methods to animal studies for the evaluation of topical/transdermal drug delivery systems” are important both for medicine and cosmetics formulation, as the authors showed the importance to characterize the lipophilic substances, even a difficult issue in cytotoxicity assays, and the importance of permeation in cosmetics and medical products. Overall this special issue has addressed aspects concerning alternative assays applied to replace animal testing in order to assess the safety and biological activity of currently available and novel drugs and biomedical devices and contain materials that follow the topics in trends and published worldwide. This issue shows balanced viewpoints of experts contributing to minimize the use of animal tests, in an attempt to act as a primary reference for industrial, commercial and research perspective in an extensive field of science.

Head and neck squamous carcinoma (HNSCC) is the sixth most common malignant cancer in the world and it is characterized by a poor prognosis. In fact, the estimated survival rate is 5 years from diagnosis. The prognosis of the disease is significantly related to the stage in which the disease is diagnosed. Moreover, the therapies are too invasive and not very efficient, disfiguring and debilitating the survivor’s quality of life which is much compromised. Nowadays, there is not a reliable and non-invasive method for early diagnosis of oral squamous cell carcinoma and the simple visual examination of the oral cavity is characterized by low sensitivity and specificity, also because the early stages of oral carcinogenesis are not associated with clear clinical abnormalities in a significant number of patients. The current issue of “Current Topics in Medicinal Chemistry (CTMC)” is aimed at reviewing the actual knowledge regarding the HNSCC in order to cover this field with a broad series of papers. The first review was prepared by an Italian team led by Fatima Ardito, Giovanni Di Gioia, Mario Roberto Pellegrino and Lorenzo Lo Muzio. The authors describe the role of genistein as a potential anticancer agent against HNSCC. The second contribution is from Linda L. Eastham, Candace M. Howard, Premalatha Balachandran, David S. Pasco, and Pier Paolo Claudio. In this case, the authors review the role of dietary phytochemicals as an alternative approach to prevent HNSCC. The third review, led by Riccardo Concu and Maria Natalia Dias- Soeiro Cordeiro, deals with the role of the Cetuximab in the treatment of HNSCC. The fourth contribution concerns the Aurora kinase inhibitors in head and neck cancer; this work was prepared by a Chinese-Japanese team led by Guangying Qi, Jing Liu, Sisi Mi, Takaaki Tsunematsu, Shengjian Jin, Wenhua Shao, Tian Liu, Naozumi Ishimaru, Bo Tang and Yasusei Kudo. Moving on, Nicola Sgaramella and Karin Nylander review covers the topic of searching for new targets and treatments in the battle against squamous cell carcinoma of the head and neck. Concu and Cordeiro present an innovative paper dealing with the development of a new QSAR model aimed at the identification of new inhibitors for the epidermal growth factor receptor. Finally, Ardito et al. present a new in vitro study of the inhibition activity of the curcumin against squamous cell carcinoma of tongue.

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found

No Text Found