Abstract
Tuberculosis (TB) and Malaria are neglected diseases, which continue to be major causes of morbidity and mortality worldwide, killing together around 5 million people each year. Mycolic acids, the hallmark of mycobacteria, are high-molecular-weight - alkyl, β-hydroxy fatty acids. Biochemical and genetic experimental data have shown that the product of the M. tuberculosis inhA structural gene (InhA) is the primary target of isoniazid mode of action, the most prescribed anti-tubercular agent. InhA was identified as an NADH-dependent enoyl-ACP(CoA) reductase specific for long-chain enoyl thioesters and is a member of the Type II fatty acid biosynthesis system, which elongates acyl fatty acid precursors of mycolic acids. M. tuberculosis and P. falciparum enoyl reductases are targets for the development of anti-tubercular and antimalarial agents. Here we present a brief description of the mechanism of action of, and resistance to, isoniazid. In addition, data on inhibition of mycobacterial and plasmodial enoyl reductases by triclosan are presented. We also describe recent efforts to develop inhibitors of M. tuberculosis and P. falciparum enoyl reductase enzyme activity.
Keywords: Tuberculosis, mycobacteria, mycolic acids, isoniazid, InhA, enoyl reductase, drugs
Current Drug Targets
Title: Enoyl Reductases as Targets for the Development of Anti-Tubercular and Anti-Malarial Agents
Volume: 8 Issue: 3
Author(s): J. S. Oliveira, I. B. Vasconcelos, I. S. Moreira, D. S. Santos and L. A. Basso
Affiliation:
Keywords: Tuberculosis, mycobacteria, mycolic acids, isoniazid, InhA, enoyl reductase, drugs
Abstract: Tuberculosis (TB) and Malaria are neglected diseases, which continue to be major causes of morbidity and mortality worldwide, killing together around 5 million people each year. Mycolic acids, the hallmark of mycobacteria, are high-molecular-weight - alkyl, β-hydroxy fatty acids. Biochemical and genetic experimental data have shown that the product of the M. tuberculosis inhA structural gene (InhA) is the primary target of isoniazid mode of action, the most prescribed anti-tubercular agent. InhA was identified as an NADH-dependent enoyl-ACP(CoA) reductase specific for long-chain enoyl thioesters and is a member of the Type II fatty acid biosynthesis system, which elongates acyl fatty acid precursors of mycolic acids. M. tuberculosis and P. falciparum enoyl reductases are targets for the development of anti-tubercular and antimalarial agents. Here we present a brief description of the mechanism of action of, and resistance to, isoniazid. In addition, data on inhibition of mycobacterial and plasmodial enoyl reductases by triclosan are presented. We also describe recent efforts to develop inhibitors of M. tuberculosis and P. falciparum enoyl reductase enzyme activity.
Export Options
About this article
Cite this article as:
Oliveira S. J., Vasconcelos B. I., Moreira S. I., Santos S. D. and Basso A. L., Enoyl Reductases as Targets for the Development of Anti-Tubercular and Anti-Malarial Agents, Current Drug Targets 2007; 8 (3) . https://dx.doi.org/10.2174/138945007780058942
DOI https://dx.doi.org/10.2174/138945007780058942 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...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
-
A Universal, Fully Automated High Throughput Screening Assay for Pyrophosphate and Phosphate Release from Enzymatic Reactions
Combinatorial Chemistry & High Throughput Screening Trypanosomatid Parasites Causing Neglected Diseases
Current Medicinal Chemistry Curcumin: A Dietary Phytochemical for Targeting the Phenotype and Function of Dendritic Cells
Current Medicinal Chemistry Reverse Vaccinology: An Epitope Based Approach to Design Vaccines
Current Bioinformatics One-Pot Glycosylation Strategy for Rapid Access of Oligosaccharides with Wide Range of Molecular Diversity
Current Organic Chemistry A Clinical Scoring System as Useful as FNAC in the Diagnosis of Tuberculous Lymphadenitis in HIV Positive Patients
Current HIV Research “Big Three” Infectious Diseases: Tuberculosis, Malaria and HIV/AIDS
Current Topics in Medicinal Chemistry Effect of Low Dose Oral Vitamin-D and Calcium Replacement in HIV Patients
Recent Patents on Anti-Infective Drug Discovery G-Protein Coupled Receptors (GPCRs): A Comprehensive Computational Perspective
Combinatorial Chemistry & High Throughput Screening Antimicrobial and Biofilm Inhibiting Diketopiperazines
Current Medicinal Chemistry MiR-147: Functions and Implications in Inflammation and Diseases
MicroRNA Currently Used Biologic Agents in the Management of Behcet’s Syndrome
Current Medicinal Chemistry Structural and Binding Properties of the Active Cell Wall Hydrolase RipA from <i>M. tuberculosis</i>, a Promising Biosensing Molecule for Early Warning Bacterial Detection
Current Medicinal Chemistry Polymer Particulates in Drug Delivery
Current Pharmaceutical Design Different Methods for Molecular and Rapid Detection of Human Novel Coronavirus
Current Pharmaceutical Design Translation Controlled mRNAs: New Drug Targets in Infectious Diseases?
Infectious Disorders - Drug Targets The Mechanistic Targets of Antifungal Agents: An Overview
Mini-Reviews in Medicinal Chemistry Thioridazine: Alternative and Potentially Effective Therapy of the XDRTB Patient
Letters in Drug Design & Discovery Mode Action Prediction of Butein as Antibacterial Oral Pathogen against <i>Enterococcus faecalis</i> ATCC 29212 and an Inhibitor of MurA Enzyme: In Vitro and In Silico Study
Letters in Drug Design & Discovery Synthesis of 99mTc-Rifabutin: A Potential Tuberculosis Radiodiagnostic Agent
Infectious Disorders - Drug Targets