title: Recent progress in the identification and development of InhA direct inhibitors of Mycobacterium tuberculosis.
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 3D-structures of InhA in drug design process.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing210009, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Lu
authors.forename: Q D
authors.initials: QD
authors.lastname: You
authors.forename: Y D
authors.initials: YD
authors.lastname: Chen
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D007538:Isoniazid / Q000031:analogs & derivatives / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009243:NAD / Q000031:analogs & derivatives / Q000494:pharmacology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology; D014260:Triclosan / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D009243:NAD; D014260:Triclosan; D010088:Oxidoreductases; C085257:InhA protein, Mycobacterium; D007538:Isoniazid