鉴定含有六氢吡咯并[3,4-]吡咯部分的苯并噻唑类化合物作为抗多药耐药结核分枝杆菌的抗结核药物。
Identification of benzothiazones containing a hexahydropyrrolo[3,4-]pyrrol moiety as antitubercular agents against MDR-MTB.
作者信息
Ma Xican, Han Bing, Wang Aoyu, Yang Lu, Huang Menghao, Chowdhury Kushan, Gu Jian, Zhang Kai, Lv Kai
机构信息
College of Pharmacy, Southwest Minzu University Chengdu 610041 China
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing 100050 China.
出版信息
RSC Adv. 2020 Apr 7;10(24):14410-14414. doi: 10.1039/d0ra00750a. eCollection 2020 Apr 6.
IMB1603, a spiro-benzothiazone compound discovered by our lab, displayed potent anti-MTB activity and . In this study, we reported a series of new BTZs containing the hexahydropyrrolo[3,4-]pyrrol moiety based on the structure of IMB1603. Among them, BTZs 11 and 24 displayed potent anti-MTB (MIC < 0.035 μM) and MDR-MTB (MIC, 0.053-0.102 μM) activity, good solubility (1.82-1.85 μg mL), and low cytotoxicity (CC > 200 μM), suggesting BTZs 11 and 24 may serve as promising candidates for further study. The molecular docking study of 11 toward DprE was also investigated, and revealed that 11 mimicked the binding pattern of PBTZ169 in the active site of DprE1.
IMB1603是我们实验室发现的一种螺苯并噻唑化合物，具有强大的抗结核分枝杆菌活性。在本研究中，我们基于IMB1603的结构报道了一系列含有六氢吡咯并[3,4 -]吡咯部分的新型苯并噻唑类化合物。其中，苯并噻唑类化合物11和24表现出强大的抗结核分枝杆菌（最低抑菌浓度<0.035 μM）和耐多药结核分枝杆菌（最低抑菌浓度，0.053 - 0.102 μM）活性、良好的溶解性（1.82 - 1.85 μg/mL）以及低细胞毒性（细胞毒性浓度>200 μM），这表明苯并噻唑类化合物11和24可能是有前景的进一步研究候选物。还对11与DprE进行了分子对接研究，结果显示11在DprE1的活性位点模拟了PBTZ169的结合模式。
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