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

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• 作者：Mery Santivañ ; ez-Veliz^a ; ^b ; Silvia Pé ; rez-Silanes^a ; ^b ; Enrique Torres^a ; Elsa Moreno-Viguri^a ; ^b ; ^{emviguri@unav.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：TB ; tuberculosis ; M. Tb. ; Mycobacterium tuberculosis ; BTG ; BacTiter-Glo microbial cell viability assay ; MDG ; Millennium Development Goals ; BFX ; benzofuroxan ; NRP ; non-replicating persistence ; MBC ; Minimal bactericidal concentration ; LORA ; Low Oxygen Recovery Assay ; SDR ; single drug-resistant ; FBS ; bovine serum ; NA ; not available ; RIF ; rifampin ; INH ; isoniazid ; OFX ; ofloxacin
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 May 2016
• 年：2016
• 卷：26
• 期：9
• 页码：2188-2193
• 全文大小：1196 K

文摘

Twenty-four quinoxaline derivatives were evaluated for their antimycobacterial activity using BacTiter-Glo microbial cell viability assay. Five compounds showed MIC values <3.1 μM and IC₅₀ values <1.5 μM in primary screening and therefore, they were moved on for further evaluation. Compounds 21 and 18 stand out, showing MIC values of 1.6 μM and IC₅₀ values of 0.5 and 1.0 μM, 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.