Targeting FtsZ for antituberculosis drug discovery: Noncytotoxic taxanes as novel antituberculosis agents
Targeting FtsZ for antituberculosis drug discovery: Noncytotoxic taxanes as novel antituberculosis agents
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DOI：
10.1021/jm050920y
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发表时间：
2006-01-26
影响因子：
7.3
通讯作者：
Ojima, I
中科院分区：
文献类型：
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作者：
Huang, Q;Kirikae, F;Ojima, I
对120个紫杉烷进行筛选，确定了一些具有显著抗结核活性的化合物。对选定的化合物进行合理优化后发现，C-赛科紫杉烷多药耐药(MDR)逆转剂(C-赛科-tras)在溶解度和检测上限(>；80亩M)下是无细胞毒性的，而对耐药和药物敏感菌株(MTB)的MIC99值保持在1.25-2.5亩M。在MIC时用TRA 3AA和10a处理MTB细胞可引起细胞的丝状化和延长，这是对FtsZ失活的表型反应。
Screening of 120 taxanes identified a number of compounds that exhibited significant antituberculosis activity. Rational optimization of selected compounds led to the discovery that the C-seco-taxane-multidrug-resistance (MDR) reversal agents (C-seco-TRAs) are non-cytotoxic at the upper limit of solubility and detection (> 80 mu M), while maintaining MIC99 values of 1.25-2.5 mu M against drug-resistant and drug-sensitive strains of Mycobacterium tuberculosis (MTB). Treatment of MTB cells with TRA 3aa and 10a at the MIC caused filamentation and prolongation of the cells, a phenotypic response to FtsZ inactivation.