Abstract
The InhA-related enoyl-ACP reductase, an enzyme involved in fatty acid synthesis, is one of the best validated targets for the development of anti-tubercular agents. However, the majority of isoniazid (INH)-resistant clinical strains are observed mainly due to the emergence of KatG mutants that do not form an INH-NAD adduct. Thus compounds that directly inhibit InhA avoiding activation by KatG would be promising candidates for combating MDR-TB. Herein, some predominant examples of InhA direct inhibitors recently developed are reviewed and special attention is paid to 3Dstructures of InhA in drug design process.
Keywords: InhA, Anti-tubercular agents, Isoniazid, KatG, INH-NAD adduct, Indirect inhibitors, Direct inhibitors, Drug design
Mini-Reviews in Medicinal Chemistry
Title: Recent Progress in the Identification and Development of InhA Direct Inhibitors of Mycobacterium tuberculosis
Volume: 10 Issue: 3
Author(s): X.Y. Lu, Q.D. You and Y.D. Chen
Affiliation:
Keywords: InhA, Anti-tubercular agents, Isoniazid, KatG, INH-NAD adduct, Indirect inhibitors, Direct inhibitors, Drug design
Abstract: The InhA-related enoyl-ACP reductase, an enzyme involved in fatty acid synthesis, is one of the best validated targets for the development of anti-tubercular agents. However, the majority of isoniazid (INH)-resistant clinical strains are observed mainly due to the emergence of KatG mutants that do not form an INH-NAD adduct. Thus compounds that directly inhibit InhA avoiding activation by KatG would be promising candidates for combating MDR-TB. Herein, some predominant examples of InhA direct inhibitors recently developed are reviewed and special attention is paid to 3Dstructures of InhA in drug design process.
Export Options
About this article
Cite this article as:
Lu X.Y., You Q.D. and Chen Y.D., Recent Progress in the Identification and Development of InhA Direct Inhibitors of Mycobacterium tuberculosis, Mini-Reviews in Medicinal Chemistry 2010; 10 (3) . https://dx.doi.org/10.2174/138955710791185064
DOI https://dx.doi.org/10.2174/138955710791185064 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...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
Related Articles
-
Structure-Based Virtual Ligand Screening: Recent Success Stories
Combinatorial Chemistry & High Throughput Screening Synthesis and Biological Evaluation of Arylthiourea Derivatives with Antitubercular Activity
Letters in Drug Design & Discovery Nebulizable Cycloserine Loaded PLGA Nanoparticles: Formulation Design, in vitro Evaluation and Stability Studies
Current Nanomedicine The Possible Potency of Ocimum basilicum New Constituent on Glucosestimulated Insulin Secretion In Vitro and β-cell Function In Vivo
Letters in Drug Design & Discovery Structural Characterization, Biological Effects, and Synthetic Studies on Xanthones from Mangosteen (Garcinia mangostana), a Popular Botanical Dietary Supplement
Mini-Reviews in Organic Chemistry Investigation of Antituberculosis from Medicinal Plant of Community Ethnic in South Sulawesi
Infectious Disorders - Drug Targets Nitric Oxide: Friendly Rivalry in Tuberculosis
Current Signal Transduction Therapy Current and Future Pharmaceutical Therapy for Rheumatoid Arthritis
Current Pharmaceutical Design Toll-Like Receptors and their Role in Renal Pathologies
Inflammation & Allergy - Drug Targets (Discontinued) Genetic Insights into Sepsis: What have we Learned and How will it Help?
Current Pharmaceutical Design Anti-TNF and Crohns Disease: When Should We Stop?
Current Drug Targets WITHDRAWN: Current Trends in the Detection of Biological Proteins and Immunological Assays using Graphene Quantum Dots
Current Analytical Chemistry Majra Honey Abrogated the Normal and Cancer Cells Proliferation Inhibition by Juniperus procera Extract and Extract/Honey Generated AgNPs
Anti-Cancer Agents in Medicinal Chemistry Importance of Pharmacology Knowledge by Dieticians
Current Nutrition & Food Science The Role of Infections in the Pathogenesis of Autoimmune Diseases
Current Drug Targets - Inflammation & Allergy Diagnostic, Prognostic and Therapeutic Potential of Heat Shock Proteins in Schistosomiasis and Bladder Cancer: A Review
Letters in Drug Design & Discovery Microwave-Assisted Multicomponent Reactions: Rapid and Regioselective Formation of New Extended Angular Fused Aza-Heterocycles
Combinatorial Chemistry & High Throughput Screening Optimal Antibiotic Therapy in the Management of the Lung of the Critically Ill
Current Respiratory Medicine Reviews Editorial (Thematic Issue: Biomarkers of Impaired Innate and Adaptive Immunity in Health and Disease)
Current Immunology Reviews (Discontinued) New Chalcones Containing Nucleosides Exhibiting In Vitro Anti-cancer Activities
Letters in Organic Chemistry