title: Antitubercular activity of 1,2,3-triazolyl fatty acid derivatives.
abstract: A collection of 1,2,3-triazoles unsaturated fatty acid mimics were efficiently synthesized by click chemistry. The 1,4-disubstituted analogs prepared covered different alkyl chain lengths and triazole positions. The compounds were subsequently tested against Mycobacterium tuberculosis, being most of them active with some of the analogs displaying activity at micromolar concentration. The most potent member of the series has the triazole moiety on the C-2 position with a carbon chain of eight or ten carbon atoms. The 1,5-isomers of the most active analog were significantly less active than the original isomer. The activity of the selected hit was assayed on several clinical MTB multi-drug resistant strains providing the same MIC.
authors.affiliation: Instituto de Química Rosario, UNR, CONICET, Suipacha 531, S2002LRK, Rosario, Argentina.
authors.forename: Diego G
authors.initials: DG
authors.lastname: Ghiano
authors.affiliation: Cátedra de Microbiología, Virología y Parasitología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, S2002KTR, Rosario, Argentina.
authors.forename: Agustina
authors.initials: A
authors.lastname: de la Iglesia
authors.affiliation: Institute of Chemical Biology & Drug Discovery, Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Liu
authors.affiliation: Institute of Chemical Biology & Drug Discovery, Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Tonge
authors.affiliation: Consejo de Investigaciones, Universidad Nacional de Rosario, Argentina; Laboratorio de Microbiología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, S2002KTR, Rosario, Argentina.
authors.forename: Héctor R
authors.initials: HR
authors.lastname: Morbidoni
authors.affiliation: Instituto de Química Rosario, UNR, CONICET, Suipacha 531, S2002LRK, Rosario, Argentina; Departamento de Química Orgánica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK, Rosario, Argentina. Electronic address: labadie@iquir-conicet.gov.ar.
authors.forename: Guillermo R
authors.initials: GR
authors.lastname: Labadie
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D057930:Click Chemistry; D018432:Drug Resistance, Multiple / Q000187:drug effects; D005227:Fatty Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D005227:Fatty Acids; D014230:Triazoles
keywords: 1,2,3-triazoles; ADME-tox; Parallel solution synthesis; Resistant strains; SAR; Tuberculosis