Da Chenxiao, Telang Nakul, Hall Kayleigh, Kluball Emily, Barelli Peter, Finzel Kara, Jia Xin, Gupton John T, Mooberry Susan L, Kellogg Glen E
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.
Medchemcomm. 2013;4(2):417-421. doi: 10.1039/C2MD20320K.
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.
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。