Abstract
Strategies for the development of novel tuberculosis chemotherapeutics against existing drug resistant strains involve the identification and inhibition of novel drug targets as well as the design and synthesis of compounds against historical targets. InhA, the enoyl reductase from the mycobacterial type II fatty acid biosynthesis pathway, is a target of the frontline chemotherapeutic, isoniazid (INH). Importantly, the majority of INH-resistant clinical isolates arise from mutations in KatG, the enzyme responsible for activating isoniazid, into its active form. Thus compounds that inhibit InhA without first requiring KatG activation will be active against the majority of INH resistant strains of Mycobacterium tuberculosis. This review describes the role of InhA in cell wall biosynthesis and recent progress in the development of novel diphenyl ether-based InhA inhibitors that have activity against both sensitive and drug resistant strains of M. tuberculosis.
Keywords: InhA, enoyl reductase, fatty acid biosynthesis, mycolic acid, cell wall, mycobacterium, isoniazid, diphenyl ether, triclosan
Current Topics in Medicinal Chemistry
Title: Development of Modern InhA Inhibitors to Combat Drug Resistant Strains of Mycobacterium tuberculosis
Volume: 7 Issue: 5
Author(s): Peter J. Tonge, Caroline Kisker and Richard A. Slayden
Affiliation:
Keywords: InhA, enoyl reductase, fatty acid biosynthesis, mycolic acid, cell wall, mycobacterium, isoniazid, diphenyl ether, triclosan
Abstract: Strategies for the development of novel tuberculosis chemotherapeutics against existing drug resistant strains involve the identification and inhibition of novel drug targets as well as the design and synthesis of compounds against historical targets. InhA, the enoyl reductase from the mycobacterial type II fatty acid biosynthesis pathway, is a target of the frontline chemotherapeutic, isoniazid (INH). Importantly, the majority of INH-resistant clinical isolates arise from mutations in KatG, the enzyme responsible for activating isoniazid, into its active form. Thus compounds that inhibit InhA without first requiring KatG activation will be active against the majority of INH resistant strains of Mycobacterium tuberculosis. This review describes the role of InhA in cell wall biosynthesis and recent progress in the development of novel diphenyl ether-based InhA inhibitors that have activity against both sensitive and drug resistant strains of M. tuberculosis.
Export Options
About this article
Cite this article as:
Tonge J. Peter, Kisker Caroline and Slayden A. Richard, Development of Modern InhA Inhibitors to Combat Drug Resistant Strains of Mycobacterium tuberculosis, Current Topics in Medicinal Chemistry 2007; 7 (5) . https://dx.doi.org/10.2174/156802607780059781
DOI https://dx.doi.org/10.2174/156802607780059781 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
- 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
-
A Novel Functional Macrophage Differentiated from Monocytes by Co- Stimulation with IL-12 and IL-18
Current Immunology Reviews (Discontinued) QSAR and Docking Studies on Propenone Derivatives as Dual COX and 5- LOX Inhibitors
Letters in Organic Chemistry Microbial Metabolomics
Current Genomics Recent Patents of Gene Sequences Relative to DNA Polymerases
Recent Patents on DNA & Gene Sequences Traditional Chinese Medicine - Sea Urchin
Mini-Reviews in Medicinal Chemistry Synthesis of Novel and Highly Functionalized 4-hydroxycoumarin Chalcone and their Pyrazoline Derivatives as Anti-Tuberculosis Agents
Letters in Drug Design & Discovery Applications of Stripping Voltammetry at Carbon Paste and Chemically Modified Carbon Paste Electrodes to Pharmaceutical Analysis
Current Pharmaceutical Analysis Melatonin and Respiratory Diseases: A Review
Current Topics in Medicinal Chemistry Mouse Models of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Current Pharmaceutical Design Extrapulmonary Sarcoidosis: A Chameleon Disease at Imaging
Current Medical Imaging 3D-QSAR and Molecular Docking Studies of Pyrazole Derivatives as Inhibitors of Enoyl Acyl Carrier Protein Reductase from Mycobacterium tuberculosis
Letters in Drug Design & Discovery Adherence to Anti-Retroviral Therapy in North Central Nigeria
Current HIV Research New Lead Structures in Antifungal Drug Discovery
Current Medicinal Chemistry Current Status of Anti-Tuberculosis Therapy: A Patent Analysis
Recent Patents on Anti-Infective Drug Discovery Micronutrient Deficiency in Pulmonary Tuberculosis - Perspective on Hepatic Drug Metabolism and Pharmacokinetic Variability of First-line Anti- Tuberculosis Drugs: Special Reference to Fat-soluble Vitamins A, D, & E and Nutri-epigenetics
Drug Metabolism Letters Single Amino Acid Repeats Connect Viruses to Neurodegeneration
Current Drug Discovery Technologies Enhancement of Immunoprotective Effect of CpG-ODN by Formulation with Polyphosphazenes Against E. coli Septicemia in Neonatal Chickens
Current Drug Delivery A Compendium of Volatile Organic Compounds (VOCs) Released By Human Cell Lines
Current Medicinal Chemistry Biomarker Metabolite Signatures Pave the Way for Electronic-nose Applications in Early Clinical Disease Diagnoses
Current Metabolomics Unified Multi-target Approach for the Rational in silico Design of Anti-bladder Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry