Synthesis, 3D-QSAR analysis and biological evaluation of quinoxaline 1,4-di-N-oxide derivatives as antituberculosis agents

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• 作者：Yuanhu Pan^a ; Panpan Li^a ; Shuyu Xie^a ; Yanfei Tao^a ; Dongmei Chen^a ; Menghong Dai^b ; Haihong Hao^b ; Lingli Huang^b ; Yulian Wang^b ; Liye Wang^a ; Zhenli Liu^b ; Zonghui Yuan^a ; ^b ; ^{yuan5802@mail.hzau.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Quinoxaline 1 ; 4-di-N-oxide ; Tuberculosis ; Antimycobacterial activity ; 3D-QSAR ; CoMFA ; CoMSIA
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 August 2016
• 年：2016
• 卷：26
• 期：16
• 页码：4146-4153
• 全文大小：3376 K

文摘

A series of quinoxaline 1,4-di-N-oxide derivatives variously substituted at C-2 position were synthesized and evaluated for in vitro antimycobacterial activity. Seventeen compounds exhibited potential activity (MIC ⩽6.25 μg/mL) against Mycobacterium tuberculosis (H37Rv), in particular the compounds 3d and 3j having an MIC value of 0.39 μg/mL. None of the compounds exhibited cytotoxicity when using an MTT assay in VERO cells. To further investigate the structure–activity relationship, CoMFA (q² = 0.507, r² = 0.923) and CoMSIA (q² = 0.665, r² = 0.977) models were performed on the basis of antimycobacterial activity data. The 3D-QSAR study of these compounds can provide useful information for further rational design of novel quinoxaline 1,4-di-N-oxides for treatment of tuberculosis.