开发基于吡咯的抗微管蛋白剂的新型C-4类似物：秋水仙碱位点中微弱但关键的氢键作用
Developing novel C-4 analogues of pyrrole-based antitubulin agents: weak but critical hydrogen bonding in the colchicine site.
作者信息
Da Chenxiao, Telang Nakul, Hall Kayleigh, Kluball Emily, Barelli Peter, Finzel Kara, Jia Xin, Gupton John T, Mooberry Susan L, Kellogg Glen E
机构信息
Department of Medicinal Chemistry & Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia, USA 23298-0540.
Department of Chemistry, Gottwald Center for the Sciences, University of Richmond, Richmond, Virginia, USA 23173.
出版信息
Medchemcomm. 2013;4(2):417-421. doi: 10.1039/C2MD20320K.
Abstract
The synthesis, biological evaluation and molecular modeling of a series of pyrrole compounds related to 3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid that evaluates and optimizes C-4 substituents are reported. The key factor for microtubule depolymerization activity appears to be the presence of an appropriately positioned acceptor for Cys241β in the otherwise hydrophobic subpocket A.
摘要
报道了一系列与3,5-二溴-4-(3,4-二甲氧基苯基)-1H-吡咯-2-羧酸相关的吡咯化合物的合成、生物学评价及分子模拟，该研究对C-4取代基进行了评估和优化。微管解聚活性的关键因素似乎是在原本疏水的亚口袋A中存在一个位置合适的Cys241β受体。
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本文引用的文献
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Pyrrole-Based Antitubulin Agents: Two Distinct Binding Modalities are Predicted for C-2 Analogs in the Colchicine Site.基于吡咯的抗微管蛋白剂：预测秋水仙碱位点的C-2类似物存在两种不同的结合模式。
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