Synthesis, antimycobacterial and cytotoxic activity of α,β-unsaturated amides and 2,4-disubstituted oxazoline derivatives.

Research paper by Francisco G FG Avalos-Alanís, Eugenio E Hernández-Fernández, Pilar P Carranza-Rosales, Susana S López-Cortina, Jorge J Hernández-Fernández, Mario M Ordóñez, Nancy E NE Guzmán-Delgado, Alejandro A Morales-Vargas, Víctor M VM Velázquez-Moreno, María G MG Santiago-Mauricio

Indexed on: 25 Jan '17Published on: 25 Jan '17Published in: Bioorganic & Medicinal Chemistry Letters


The synthesis of six α,β,-unsaturated amides and six 2,4-disubstituted oxazolines derivatives and their evaluation against two Mycobacterium tuberculosis strains (sensitive H37Rv and a resistant clinical isolate) is reported. 2,4-Disubstituted oxazolines (S)-3b,d,e were the most active in the sensitive strain with a MIC of 14.2, 13.6 and 10.8μM, respectively, and the compounds (S)-3d,f were the most active against resistant strain with a MIC of 6.8 and 7.4μM. The ex-vivo evaluation of hepatotoxicity on precision-cut rat liver slices was also tested for the α,β-unsaturated amides (S)-2b and (S)-2d,f and for the oxazolines (S)-3b and (S)-3d,f at different concentrations (5, 15 and 30μg/mL). The results indicate that these compounds possess promising antimycobacterial activity and at the same time are not hepatotoxic. These findings open the possibility for development of new drugs against tuberculosis.