title: Synthesis and biological activities of triazole derivatives as inhibitors of InhA and antituberculosis agents.
abstract: InhA, the enoyl reductase from the mycobacterial type II fatty acid biosynthesis pathway, is a target for the development of novel drugs against tuberculosis. We exploited copper-catalyzed [3+2] cycloaddition between alkynes and different azides to afford 1,4-disubstituted triazole or α-ketotriazole derivatives. Several compounds bearing a lipophilic chain mimicking the substrate were able to inhibit InhA. Among them, 1-dodecyl-4-phenethyl-1H-1,2,3-triazole displayed a minimum inhibitory concentration inferior to 2 μg/mL against Mycobacterium tuberculosis H37Rv.
authors.affiliation: CNRS, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, LSPCMIB, UMR-5068, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Menendez
authors.forename: Sylvain
authors.initials: S
authors.lastname: Gau
authors.forename: Christian
authors.initials: C
authors.lastname: Lherbet
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rodriguez
authors.forename: Cyril
authors.initials: C
authors.lastname: Inard
authors.forename: Maria Rosalia
authors.initials: MR
authors.lastname: Pasca
authors.forename: Michel
authors.initials: M
authors.lastname: Baltas
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020134:Catalytic Domain; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014260:Triclosan / Q000737:chemistry
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D014230:Triazoles; D014260:Triclosan; D010088:Oxidoreductases; C085257:InhA protein, Mycobacterium