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

被引:17
作者
Avalos-Alanis, Francisco G. [1 ]
Hernandez-Fernandez, Eugenio [1 ]
Carranza-Rosales, Pilar [2 ]
Lopez-Cortina, Susana [1 ]
Hernandez-Fernandez, Jorge [1 ]
Ordonez, Mario [3 ]
Guzman-Delgado, Nancy E. [4 ]
Morales-Vargas, Alejandro [5 ]
Velazquez-Moreno, Victor M. [5 ]
Santiago-Mauricio, Maria G. [2 ]
机构
[1] Univ Autonoma Nuevo Leon, Fac Ciencias Quim, Pedro de Alba S-N,Ciudad Univ, San Nicolas De Los Garza 66400, Nuevo Leon, Mexico
[2] Inst Mexicano Seguro Social, Ctr Invest Biomed Noreste, Monterrey, Nuevo Leon, Mexico
[3] Univ Autonoma Estado Morelos, Ctr Invest Quim IICBA, Ave Univ 1001, Cuernavaca 62209, Morelos, Mexico
[4] Inst Mexicano Seguro Social, Unidad Med Alta Especialidad 34, Monterrey 64730, Nuevo Leon, Mexico
[5] Secretaria Salud, Lab Estatal Salud Publ, Guadalupe 67180, Nuevo Leon, Mexico
关键词
Organic synthesis; Unsaturated amides; alpha,beta-2,4-Disubstituted oxazolines; Antimycobacterial activity; Hepatotoxic activity; DRUG; AGENTS; INHIBITORS;
D O I
10.1016/j.bmcl.2017.01.024
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The synthesis of six alpha,beta,-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 mu M, respectively, and the compounds (S)-3d,f were the most active against resistant strain with a MIC of 6.8 and 7.4 mu M. The ex-vivo evaluation of hepatotoxicity on precision-cut rat liver slices was also tested for the alpha,beta-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 mu g/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. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:821 / 825
页数:5
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