Design and application of a rigid quinazolone scaffold based on two-face Bim alpha-helix mimicking
Design and application of a rigid quinazolone scaffold based on two-face Bim alpha-helix mimicking
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基于二面Bim α螺旋模拟的刚性喹唑酮支架的设计与应用
DOI：
10.1016/j.ejmech.2013.09.030
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发表时间：
2013
影响因子：
6.7
通讯作者：
Sheng Hongkun
中科院分区：
文献类型：
--
作者：
Zhang Zhichao;Liang Xiaomeng;Li Xiangqian;Song Ting;Chen Qingbin;Sheng Hongkun
基于我们先前发现的模拟Bim α-螺旋两面的蒽醌骨架，我们通过结构简化和优化得到了喹唑酮骨架。据推测，刚性双环是必要的和有效的，以维持双面结合模式。在此基础上合成了一种新型的双结合剂6c [6，7，8-三羟基-3-（2-羟基-5-甲基苄基）-2-苯基喹唑啉-4（3 H）-酮]，其对Mcl-1和Bcl-2的Ki值分别为0.123 μM和0.179 μM。
Based on our previous discovery of an anthraquinone scaffold mimicking two faces of Bim α-helix, we derived a quinazolone scaffold through structure simplification and optimization. It was inferred that a rigid bicyclic ring was necessary and efficient to maintain the two-faced binding mode. A novel dual inhibitor6c[6,7,8-trihydroxy-3-(2-hydroxy-5-methylbenzyl)-2-phenylquinazolin-4(3H)-one] was obtained based on this scaffold.6cexhibited dual binding activity withKivalues of 0.123 μM for Mcl-1 and 0.179 μM for Bcl-2.