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

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• 作者：Francisco G. Avalos-Alaní ; s^a ; Eugenio Herná ; ndez-Ferná ; ndez^a ; ^{eugenio.hernandezfr@uanl.edu.mx} ; Pilar Carranza-Rosales^b ; ^{pilarcarranza@cibinmty.net} ; Susana Ló ; pez-Cortina^a ; Jorge Herná ; ndez-Ferná ; ndez^a ; Mario Ordó ; ñ ; ez^c ; Nancy E. Guzmá ; n-Delgado^d ; Alejandro Morales-Vargas^e ; Ví ; ctor M. Velá ; zquez-Moreno^e ; Marí ; a G. Santiago-Mauricio^b
• 关键词：Organic synthesis ; Unsaturated amides ; α ; β-2 ; 4-Disubstituted oxazolines ; Antimycobacterial activity ; Hepatotoxic activity
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：27
• 期：4
• 页码：821-825
• 全文大小：1206 K
• 卷排序：27

文摘

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 10.8 μM, respectively, and the compounds (S)-3d,f were the most active against resistant strain with a MIC of 6.8 and 7.4 μM. 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 30 μg/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.