基于Topomer CoMFA方法的2-哌嗪基噻唑羟肟酸类化合物的三维定量构效关系研究  

3D-QSAR studies of 2-piperazinyl thiazole hydroxamic acids based on Topomer CoMFA method

作　　者：梁经纬[1] 李佐静[2] 张廷剑[1] 袁伟燕[1] 闫心丽[2] 王琳[1] 孟繁浩[1] 

机构地区：[1]中国医科大学药学院,辽宁沈阳110001 [2]沈阳药科大学医疗器械学院,辽宁沈阳110016

出　　处：《计算机与应用化学》2013年第7期781-784,共4页Computers and Applied Chemistry

基　　金：辽宁省自然科学基金(201202247);国家自然科学基金(30571591;81274182)资助

摘　　要：组蛋白去乙酰化酶是分子靶向抗肿瘤药物的一个重要靶点,目前大多数组蛋白去乙酰化酶抑制剂都属于羟肟酸类化合物。本实验利用Tripo公司的Sybyl-X软件包,采用Topomer CoMFA方法对2-哌嗪基噻唑类羟肟酸类化合物进行了三维定量构故关系分析(3D-QSAR):首先选择在该系列化合物都含有的哌嗪环与噻唑环之间做切割,生成含有公共骨架的R1基团和R2基团,再利用计算机分别自动叠合R1基团和R2基团,并计算立体场和静电场大小,最后得到了该类化合物作为组蛋白去乙酰化酶抑制剂的3D-QSAR模型,q^2=0.561,r^2=0.870。该模型预测结果良好,可以用于设计新型组蛋白去乙酰化酶抑制剂。Histone deacetylase is an important target for molecular targeted anticancer drugs. Currently, major historic deacetylase inhibitors have the chemical Skeleton of hydroxamic acids, we used Sybyl-X package of Tripe company, to build the three-dimensional quantitative structure-activity relationship （3D-QSAR） model of these 2-piperazinyl thiazole hydroxamic acids with Topomer CoMFA method： firstly, cut the series of compounds between a piperazine ring and a thiazole ring which all compounds contain,generating public skeleton containing R1 group and R2 groups, then they were automatically superimposed by computer, with the value of steric and electrostatic field being figured out,finally get the 3D-QSAR model with q2= 0.561, r2 = 0.870. The model predicts well that it can be used to design novel histone deacetylase inhibitor.

关 键 词：三维定量构效关系(3D-QSAR) 2-哌嗪基噻唑类羟肟酸 组蛋白去乙酰化酶(HDAC) Topomer COMFA 新药设计 

分 类 号：O641[理学—物理化学]