Abstract
The global tuberculosis epidemic and emergence of drug resistance call for intensive research on new antimycobacterial agents. Recent development is focused mainly on heterocyclic molecules. In many cases, introduction of sulphur has improved antimicrobial activity; many drugs feature a sulphur heterocycle. Thiophene derivatives and thiadiazoles including derived ortho-condensed heterocycles have been found to have a wide range of biological activities. This review highlights the recent progress in the field with a focus on whole-cell antimycobacterial activity of the agents as well as targeting of enzymes from Mycobacterium tuberculosis. Some of the compounds have exhibited high activity with submicromolar minimum inhibitory concentrations including activity against drug-resistant strains and/or IC50 values for a range of enzymes as their targets (InhA, dehydroquinase, Pks13, carbonic anhydrases, DprE1). Mechanisms of action, toxicity, and structure-activity relationships are also discussed. Several compounds have exhibited promising in vitro and in vivo activities and safety profiles, thus constituting novel, promising leads.
Keywords: Antimycobacterial activity, Enzyme inhibition, Heterocycles, Mycobacterium tuberculosis, Sulphur, Thiophene, Thiadiazole.
Current Topics in Medicinal Chemistry
Title:Sulphur-Containing Heterocycles as Antimycobacterial Agents: Recent Advances in Thiophene and Thiadiazole Derivatives
Volume: 16 Issue: 26
Author(s): Martin Krátký and Jarmila Vinsova
Affiliation:
Keywords: Antimycobacterial activity, Enzyme inhibition, Heterocycles, Mycobacterium tuberculosis, Sulphur, Thiophene, Thiadiazole.
Abstract: The global tuberculosis epidemic and emergence of drug resistance call for intensive research on new antimycobacterial agents. Recent development is focused mainly on heterocyclic molecules. In many cases, introduction of sulphur has improved antimicrobial activity; many drugs feature a sulphur heterocycle. Thiophene derivatives and thiadiazoles including derived ortho-condensed heterocycles have been found to have a wide range of biological activities. This review highlights the recent progress in the field with a focus on whole-cell antimycobacterial activity of the agents as well as targeting of enzymes from Mycobacterium tuberculosis. Some of the compounds have exhibited high activity with submicromolar minimum inhibitory concentrations including activity against drug-resistant strains and/or IC50 values for a range of enzymes as their targets (InhA, dehydroquinase, Pks13, carbonic anhydrases, DprE1). Mechanisms of action, toxicity, and structure-activity relationships are also discussed. Several compounds have exhibited promising in vitro and in vivo activities and safety profiles, thus constituting novel, promising leads.
Export Options
About this article
Cite this article as:
Krátký Martin and Vinsova Jarmila, Sulphur-Containing Heterocycles as Antimycobacterial Agents: Recent Advances in Thiophene and Thiadiazole Derivatives, Current Topics in Medicinal Chemistry 2016; 16 (26) . https://dx.doi.org/10.2174/1568026616666160506131118
DOI https://dx.doi.org/10.2174/1568026616666160506131118 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Peptidylprolyl Cis / Trans Isomerases (Immunophilins): Biological Diversity - Targets - Functions
Current Topics in Medicinal Chemistry Advances in Research on Pharmacological Activities and Synthesis of Oleanolic Acid Derivatives at C-3 Position
The Natural Products Journal The Changing Face of Tobacco Use Among United States Youth
Current Drug Abuse Reviews Synthesis of an Indoloquinoxaline Derivative as Potential Inhibitor of InhA enzyme of Mycobacterium tuberculosis
Letters in Organic Chemistry Lipoplexes Formulation and Optimisation: In Vitro Transfection Studies Reveal No Correlation with In Vivo Vaccination Studies
Current Drug Delivery Synthesis of spirobiindane based bis-flavanones and bis-chroman-4-ones by Kabbe Reaction
Letters in Organic Chemistry Potential Triazole-based Molecules for the Treatment of Neglected Diseases
Current Medicinal Chemistry Thalidomide Analogues as Anticancer Drugs
Recent Patents on Anti-Cancer Drug Discovery Patent Selections
Recent Patents on Anti-Infective Drug Discovery Electronic-Topological and Neural Network Approaches to the Structure- Antimycobacterial Activity Relationships Study On Hydrazones Derivatives
Medicinal Chemistry A Highly Concentrated and Taste-Improved Aqueous Formulation of Efavirenz for a More Appropriate Pediatric Management of the Anti-HIV Therapy
Current HIV Research Pre-Exposure Prophylaxis - One More Tool for HIV Prevention
Current HIV Research Targeting Toll-Like Receptor Signaling Pathways for Design of Novel Immune Therapeutics
Current Drug Discovery Technologies Staphylococcus aureus: Current State of Prevalence, Impact, and Vaccine Development
Current Pharmaceutical Design Epoxide Hydrolases and their Application in Organic Synthesis
Current Organic Chemistry Antimicrobial Precious-Metal Nanoparticles and their Use in Novel Materials
Recent Patents on Food, Nutrition & Agriculture The Immune-Endocrine-Metabolic Unit During Human Tuberculosis
Current Immunology Reviews (Discontinued) Design and Synthesis of (<i>E</i>)-4-(2-Phenyl-2<i>H</i>-chromen-3-yl)but-3-en-2-ones and Evaluation of their <i>In Vitro</i> Antimicrobial Activity
Letters in Organic Chemistry Management of Certain Respiratory Disorders through Ayurveda: A Systematic Review of Clinical Studies Published in Ayurveda Journal
Current Traditional Medicine Editorial: Comparison of Forgotten Surgical Techniques for Pulmonary Tuberculosis
Current Respiratory Medicine Reviews