2. Academic Validation
  3. Antitubercular activity of 1,2,3-triazolyl fatty acid derivatives

Antitubercular activity of 1,2,3-triazolyl fatty acid derivatives

  • Eur J Med Chem. 2017 Jan 5:125:842-852. doi: 10.1016/j.ejmech.2016.09.086.
Diego G Ghiano 1,  Agustina de la Iglesia 2,  Nina Liu 3,  Peter J Tonge 3,  Héctor R Morbidoni 4,  Guillermo R Labadie 5
Affiliations

Affiliations

  • 1 Instituto de Química Rosario, UNR, CONICET, Suipacha 531, S2002LRK, Rosario, Argentina.
  • 2 Cátedra de Microbiología, Virología y Parasitología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, S2002KTR, Rosario, Argentina.
  • 3 Institute of Chemical Biology & Drug Discovery, Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA.
  • 4 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.
  • 5 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.
PMID: 27750201 DOI: 10.1016/j.ejmech.2016.09.086
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.

Keywords

1,2,3-triazoles; ADME-tox; Parallel solution synthesis; Resistant strains; SAR; Tuberculosis.

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