Design and synthesis of novel quinoxaline derivatives as potential candidates for treatment of multidrug-resistant and latent tuberculosis

被引：29
作者：
Santivañez-Veliz, Mery [1 ,2 ]
Perez-Silanes, Silvia [1 ,2 ]
Torres, Enrique [1 ]
Moreno-Viguri, Elsa [1 ,2 ]
机构：
[1] Univ Navarra, Dept Organ & Pharmaceut Chem, Irunlarrea S-N, Pamplona 31008, Spain
[2] Univ Navarra, Inst Trop Hlth, Irunlarrea S-N, E-31008 Pamplona, Spain
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 09期
基金：
美国国家卫生研究院;
关键词：
Tuberculosis; Antimycobacterial; Quinoxaline; Intracellular activity; MYCOBACTERIUM-TUBERCULOSIS; 1,4-DI-N-OXIDE DERIVATIVES; BIOLOGICAL EVALUATION; IN-VITRO; AGENTS; ANTIMYCOBACTERIAL; DRUG; INHIBITORS; CHALCONES; ANALOGS;
D O I：
10.1016/j.bmcl.2016.03.066
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Twenty-four quinoxaline derivatives were evaluated for their antimycobacterial activity using BacTiter-Glo microbial cell viability assay. Five compounds showed MIC values < 3.1 mu M and IC50 values < 1.5 mu M in primary screening and therefore, they were moved on for further evaluation. Compounds 21 and 18 stand out, showing MIC values of 1.6 mu M and IC50 values of 0.5 and 1.0 mu M, respectively. Both compounds were the most potent against three evaluated drug-resistant strains. Moreover, they exhibited intracellular activity in infected macrophages, considering log-reduction and cellular viability. In addition, compounds 16 and 21 were potent against non-replicating Mycobacterium tuberculosis and compound 21 was bactericidal. Therefore, quinoxaline derivatives could be considered for making further advances in the future development of antimycobacterial agents. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2188 / 2193
页数：6
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