Enoyl reductases as targets for the development of anti-tubercular and anti-malarial agents
Autor: | Ícaro de Sousa Moreira, Jaim S. Oliveira, D.S. Santos, Luiz Augusto Basso, Igor B. Vasconcelos |
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Rok vydání: | 2007 |
Předmět: |
Tuberculosis
Clinical Biochemistry Antitubercular Agents Reductase Biology Microbiology Antimalarials Drug Delivery Systems Drug Discovery medicine Animals Humans Antimalarial Agent Enzyme Inhibitors Mode of action Pharmacology chemistry.chemical_classification INHA Isoniazid Fatty acid medicine.disease Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) Mechanism of action chemistry Biochemistry Drug Design Molecular Medicine medicine.symptom medicine.drug |
Zdroj: | Current drug targets. 8(3) |
ISSN: | 1873-5592 |
Popis: | 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 alpha-alkyl, beta-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. |
Databáze: | OpenAIRE |
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