Medicinal Chemistry

Medicinal chemistry deals with the discovery, design and development of drug substances along with the pharmacological and analytical characterization. Medicinal chemists are indispensable in the preclinical stages of drug development, and again as pharmaceutical chemists in drug quality control. Green chemistry is considered as frontiers of interdisciplinary science and is used to design chemical products and procedures that reduce the generation of hazardous chemical substances. Green chemistry has come a long way since its birth in 1991, growing from a small grassroot idea into a new approach to scientifically based environmental protection. It is also known as sustainable chemistry. Green chemistry applies the life cycle of a chemical product, including its manufacture, use, design, and ultimately disposal. Green chemistry is very helpful in the prevention of pollution at the molecular level and provides innovative scientific solutions. It is able to reduce the negative impacts of chemical products on human health. The main aspects of Green chemistry are; prevent waste, design less hazardous chemical synthesis, design safer chemicals and products. Green chemistry also plays an important role in the agriculture sector and has a very wide application in pharmaceutical industry in developing innovatory drug delivery methods which are less toxic and more effective with minimum side effects and could help millions of patients. At the beginning of this special issue, we called to Medicinal and Green Chemistry researchers to contribute their review articles to shed light on the above topic by touching following two subtopics: 1. Medicinal drugs for management of neurodegenerative disease, cancer, immune dysfunction and diabetes. 2. Green chemistry approaches for the management of neurodegenerative disease, cancer, immune dysfunction and diabetes. Karim et al. [1] have shed light on an increasing role of polyphenols as novel therapeutics for Alzheimer’s disorder (AD) as it is the most prevalent neurodegenerative disorder with approximately 29 million aging people suffering from this disease worldwide. This number is projected to triple by 2050. Alzheimer's is a complex and multifactorial neurodegenerative condition, characterized by complex pathology including oxidative stress, the formation of aggregates of amyloid and tau, enhanced immune responses, metal deposition and disturbances in cholinesterase enzymes. There is no effective pharmacological treatment for combating the disease to date. The ineffectiveness of current pharmacological interventions in AD has led scientists to search for more safe and effective alternative therapeutic agents. Thus, natural products have become an important avenue for drug discovery in AD research. In this connection, polyphenols are natural products that have been shown to be effective in the modulation of the type of neurodegenerative changes seen in AD, suggesting a possible therapeutic role. In their review, they focus on the chemistry of polyphenols, clinical studies for evaluating polyphenols as effective alternatives in AD treatment, cellular and molecular aspects of polyphenols in improving cognitive deficits and the current challenges and futuristic approaches to use polyphenols as safe and effective therapeutic agents in AD treatment [1]. Khan et al. [2] focused on herbal medicine for glioblastoma with respect to current and future prospects. Actually, glioblastoma is one of the most aggressive and devastating tumours of the central nervous system with short survival time. Glioblastoma usually shows fast cell proliferation and invasion to normal brain tissue causing poor prognosis. The present standard of care in patients with glioblastoma includes surgery followed by radiotherapy and temozolomide based chemotherapy. Unfortunately, these approaches are not sufficient to lead a favourable prognosis and survival rates. As the current approaches do not provide a long-term benefit in those patients, new alternative treatments, including natural compounds, have drawn attention. Due to their natural origin, they are associated with minimum cellular toxicity towards normal cells and it has become one of the most attractive approaches to treat tumours by natural compounds or phytochemicals. In their review, the role of natural compounds or phytochemicals in the treatment of glioblastoma described in the light of efficacy on various aspects of glioblastoma pathophysiology such as cell proliferation, apoptosis, cell cycle regulation, cellular signaling pathways, chemo-resistance and their role in combinatorial therapeutic approaches. Preclinical data available in the literature suggest that phytochemicals hold immense potential to be translated into treatment modalities. However, further clinical studies with conclusive results are required to implement phytochemicals in treatment modalities [2]. Mohammed has mentioned recent updates on the valuable impacts of halophytic genus Suaeda in respect to its nutritional, chemical, and biological values [3]. Suaeda is a halophytic genus belonging to the Amaranthaceae family and is able to survive in the high salted marsh areas of the world. Suaeda plants have the ability to biosynthesize natural substances with powerful antioxidant activity and are considered as a renewable source of energy, food and edible oil for a larger number of populations living in the harsh environment with high salinity and drought conditions. These plants also meet folk and alternative medicine needs. Mohammed encompassed in his review available scientific literature related to folk medicinal uses of Suaeda plants, their nutritional values and chemical constituents. In addition, the biological trials applied for the Suaeda plants are also incorporated within this review. The review covers research from major science literature search engines and other sites representing scientific literature, i.e., Scifinder, Google Scholar, PubMed, ScienceDirect, Scopus and Google. The searches were programmed on the advance options available in the search engines and are latest up to November 2019. The searches were exhaustive and rechecked for accuracy. The study summarizes the uses of Suaeda plants as a remedy for various ailments due to their contents from the polyphenols and flavonoids. The comparatively large amounts of fixed oils, minerals, and vitamins in Suaeda plants have also made them a potential renewable source for foods [3]. Fayaz et al. [4] wrote on the outcome of chemicals on amyotrophic lateral sclerosis: Is green chemistry the answer? Medicinal Chemistry has played a critical role in evolving new products, resources and processes which inexorably correspond to our high standards of living. Unfortunately, this has also caused deterioration of human health and threats to the global environment, even deaths when highly exposed to certain chemicals, whether due to improper use, mishandling or disposal. There are chemicals, which apart from being carcinogens, endocrine disruptors or neurotoxins, are also responsible for climate change and ozone depletion. Certain chemicals are known to cause neurotoxicity and are having tendencies to damage the central as well as peripheral nervous system or brain by damaging neurons or cells which are responsible for transmitting and processing of signals. This has raised serious concerns for the use and handling of such chemicals and has given the growth in a relatively new emerging field known as Green Chemistry that strives to achieve sustainability at the molecular level and has an ability to harness chemicals to meet environmental and economic goals. It has been reported in the literature that apart from family history in the aetiology of Amyotrophic lateral sclerosis (ALS), also termed as “Lou Gehrig’s disease”, a neurological disorder, environmental factors, heavy metals, particularly selenium, lead, mercury, cadmium, formaldehyde, pesticides and certain herbicides also play a role in ALS. ALS a progressive neurodegenerative disease affects motor cortex, brain stem and spinal cord, causing muscular weakness, spasticity, and hyperreflexia. In this review, Fayaz et al. discussed and summarized the evidence supporting the undesirable role of chemical substance/herbicides/pesticides in ALS aetiology and its mitigation by adopting green chemistry [4]. Sobhani et al. [5] described the therapeutic effects of Ziziphus jujuba Mill fruit in traditional and modern medicine. Ziziphus jujuba Mill belonging to the Rhamnaceae family and it has been consumed since ancient times as a medicine and food. In the different traditional medical schools, Z. jujuba has been used to treat various diseases such as respiratory system diseases (asthma, cough, and laryngitis), gastrointestinal problems (constipation, colitis and liver diseases), as well as, cardiovascular and genitourinary system diseases. From the perspective of Islamic traditional medicine, Z. jujuba fruit is an emollient, laxative, and maturative. It can purify the blood and improve blood circulation, relieve internal heat and reduce inflammation. Some therapeutic uses of Z. jujuba such as antibacterial, antioxidant, sedative, hepato-protective, anti-hyperglycemic, and antihyperlipidemic activities have been shown in modern pharmacological studies. Sobhani et al. reported traditional and ethnomedicinal uses, botany, phytochemistry and pharmacological activities of Z. jujuba in their review article [5]. This special issue was written to enable an in-depth understanding of the special issue topic. As a result, a new approach can be developed towards drug development and clinical aspects for enhanced progress in management strategies of different disorders. We wish to end this editorial by thanking Prof. Dimitra Hadjipavlou-Litina, the Editor-in-Chief, as well as Akhtar Waheed (Sr. Manager) along with all the contributing authors who have enthusiastically responded to our request in contributing in this special issue of Medicinal Chemistry. I additionally extend my thanks to all peer reviewers for their time and expertise in reviewing individual contribution. Due to team efforts of such a great scientific team-gifted with extensive experience in the arena of Medicinal and Green Chemistry, this special issue provides a scholarly and important resource of reference for the benefit of medical-researchers and those suffering from various diseases.

High-throughput sequencing techniques produce plenty of –omics data including genomics, transcriptomes, and proteomics data. These data require us developing various computational methods to understand them. The knowledge behind the data also provide us an opportunity for disease treatment. Thus, the applications of computational methods in pharmacogenomics and pharmacoproteomics have become a very hot topic in drug design, drug target discovery and disease treatment. This special issue focused on various aspects of the development and application of computational techniques in pharmacogenomics and pharmacoproteomics. Nuclear receptors are a superfamily of ligand-dependent transcription factors that are closely related to cell development, differentiation, reproduction, homeostasis and metabolism. Zhang et al. [1] summarized the application of machine learning methods in the prediction of nuclear receptors. Bacterial infection could also influence the healthy. Mycobacterium tuberculosis (MTB) can cause the terrible tuberculosis (TB), which is reported as one of the most dreadful epidemic. Li et al. [2] reviewed the progress of machine learning method application in subcellular localization of mycobacterial protein. Chen et al. [3] proposed a support vector machine-based method to identify anti-tubercular peptides. Disease therapy is the most important task for biological research. Sun et al. [4] focused on coronary heart disease. They used the method of mendelian randomization to assess the causal effect of interleukin-18 on coronary heart disease and found that Interleukin-18 is unlikely to represent even a modest casual factor for coronary heart disease risk. Zhang et al. [5] focused on insulin resistance. They performed integrative analysis of gene expression profiling and gene regulatory network to identify potential biomarkers early in the development of insulin resistance. Malik et al. [6] designed new xanthine oxidase inhibitors from natural constituents along with antioxidant potential. Wang et al. [7] identify key genes signatures during renal cell carcinoma and uncover their potential mechanisms. They predicted that some genes might be target genes for diagnosing the kidney cancer. Chen et al. [8] focused on dairy safety. They developed a computational method to assess dairy safety. In summary, all eight papers focused on pharmacogenomics and pharmacoproteomics and will provide important guide for disease therapy.

Medicinal chemistry is a discipline at the intersection of chemistry and various biological and pharmacological research areas, where system biology and cheminformatics are highly involved. System biology is a holistic approach that focused on the complex interactions within the biological systems. Cheminformatics is a combination of different working fields, including biochemistry, biophysics, and computer science. Both have increasingly been playing important roles in stimulating the development of medicinal chemistry [1-5]. The main goal of this special issue is to report recent progresses of medicinal chemistry from the angles of system biology and cheminformatics. Cells need high-sensitivity detection of non-self molecules in order to fight against pathogens. These cellular sensors are thus of significant importance to medicinal purposes, especially for treating novel emerging pathogens. IG-I-like receptors (RLRs) are intracellular sensors for viral RNAs (vRNAs). The review article titled “Structural variability in the RLR-MAVS pathway and sensitive detection of viral RNAs” by Prof. Qiu-Xing Jiang of the University of Florida in USA [6], discussed the molecular events of RLR-MAVS (mitochondrial antiviral signaling protein) pathway from the angle of detecting single copy or a very low copy number of vRNAs in the presence of non-specific competition from cytosolic RNAs, and the key structural variabilities in the RLR / vRNA complexes, the MAVS helical polymers, and the adapter-mediated interactions between the active RLR / vRNA complex, and the inactive MAVS were also reviewed. These structural variations may reflect the adaptation of the signaling pathways to different conditions or reach different levels of sensitivity in its response to exogenous vRNAs. Hyperbaric Oxygenation Therapy (HBOT) is used as an adjunctive method for multiple diseases. The review article titled “The Multiple Applications and Possible Mechanisms of the Hyperbaric Oxygenation Therapy” by Dr. Chunxia Chen and Dr. Luying Huang, and their colleagues of the People’s Hospital of Guangxi Zhuang Autonomous Region in China [7], reviewed the current applications and possible mechanisms of HBOT, and concluded that the comprehensive consideration of the advantages and the disadvantages of HBOT is required to obtain a satisfying therapeutic outcome. Information of protein subcellular localization is crucially important for both basic research and drug development [8, 9]. With the explosive growth of protein sequences discovered in the post-genomic age, it is highly demanded to develop powerful bioinformatics tools for timely and effectively identifying their subcellular localization purely based on the sequence information alone. The Research article titled “pLoc_bal-mEuk: predict subcellular localization of eukaryotic proteins by quasibalancing training dataset and PseAAC” by Professor Dr. Kuo-Chen Chou of Gordon Life Science Institute in USA [10], and his colleagues discussed the development of a new predictor termed pLoc bal-mEuk by quasi-balancing the training dataset. Cross-validation tests on exactly the same experiment-confirmed dataset have indicated that the proposed new predictor is remarkably superior as compared to pLoc-mEuk, the existing state-of-the-art predictor in identifying the subcellular localization of eukaryotic proteins. It has not escaped our notice that the quasi-balancing treatment can also be used to deal with many other biological systems. Polysialic acid (polySia) is a unique carbohydrate polymer produced on the surface of neuronal cell adhesion molecule (NCAM) in a number of cancer cells, and strongly correlates with the migration and invasion of tumor cells with aggressive propagation, metastasis and poor clinical prognosis [11]. polySia synthesis is catalyzed by two polysialyltransferases (polySTs), ST8SiaIV (PST) and ST8SiaII (STX) [12]. The research paper titled “The Inhibition of Polysialyltransferase ST8SiaIV through Heparin binding to Polysialytransferase Domain (PSTD)” by Professors Drs. Guo-Ping Zhou and Ri-Bo Huang and their colleagues of Guangxi Academy of Sciences in China [13], verified that the PSTD is the binding domain of the inhibitors of Polysialyltransferase ST8Sia IV, and further determined the binding sites between the different type of heparins, unfractionated heparin (UFH), low molecular heparin (LMWH) and heparin tetrasaccharide (DP4) and the PSTD by the fluorescence quenching analysis, the CD spectra, and NMR spectroscopy experiments. Their results indicate that each type of heparins could be bound to the specific residues in the PSTD. These important findings provided new insights into an inhibition mechanism of the polysialyltransferases and should be helpful to design more effective drugs for treatment of metastatic cancer. With the avalanche of protein sequences emerging in the post-genomic age, it is highly desirable to develop computational tools for timely and effectively identifying their subcellular localization based on the sequence information alone. The research article titled “pLoc_bal-mVirus: predict subcellular localization of virus proteins by PseAAC and balancing training dataset” by Prof. Drs. Kuo-Chen Chou (Gordon Life Science Institute, USA), and Xuan Xiao (University of Electronic Science and Technology of China) and their colleagues defined the development of a new predictor called pLoc_bal-mVirus by balancing the training dataset [14]. Cross-validation tests on exactly the same experiment-confirmed dataset have indicated that the proposed new predictor is remarkably superior to pLoc-mVirus, the existing state-of-the-art predictor in identifying the subcellular localization of virus proteins. To maximize the convenience for most experimental scientists, a user-friendly webserver for the new predictor has been established at http://www.jci-bioinfo.cn/pLoc_bal-mVirus/, by which users can easily get their desired results. It is anticipated that the proposed predictor will become a useful high throughput tool for both basic research and drug development, particularly in designing multi-target drugs [15]. Inhibiting the activity of α-amylase is an important strategy in the treatment of diabetes mellitus. Most inhibitors of α- amylase have serious adverse effects, and the α-amylase inactivation mechanisms for the design of safer inhibitors are yet to be revealed. The last research article titled “Inhibition of α-amylase activity by Zn2+: Insights from spectroscopy and molecular dynamics simulations” by Prof. Drs. Guo-Ping Zhou and Ri-Bo Huang, and their colleagues in Guangxi Academy of Sciences studied the inhibitory effect of Zn2+ on the structure and dynamic characteristics of α-amylase from Anoxybacillus sp. GXS-BL (AGXA) [16], which shares the same catalytic residues and similar structures as human pancreatic (HPA) and salivary

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