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

Abstract：

: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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Avalos-Alanís FG,Hernández-Fernández E,Carranza-Rosales P,López-Cortina S,Hernández-Fernández J,Ordóñez M,Guzmán-Delgado NE,Morales-Vargas A,Velázquez-Moreno VM,Santiago-Mauricio MG

doi

10.1016/j.bmcl.2017.01.024

subject

Has Abstract

pub_date

2017-02-15 00:00:00

pages

821-825

issue

4

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(17)30037-9

journal_volume

27

pub_type

杂志文章

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