摘要
微管蛋白对细胞增殖极为重要,现已成为抗癌药物研发的重要靶标之一。针对53个以2,5-二酮哌嗪为基本骨架的微管蛋白抑制剂,分别运用比较分子力场分析(CoMFA)以及比较分子相似性指数分析(CoMSIA)2种经典方法进行了三维定量构效关系(3D-QSAR)研究,并依次建立了相关的模型。CoMFA模型的交叉验证系数q^2为0.642,相关系数r^2为0.996:CoMSIA模型的q^2和r^2,分别为0.725,0.908。模型具有较好的预测能力和较强的稳定性。3D-QSAR模型三维等势图揭示了一些结构特征与抑制活性的关系。我们希望这些研究为该类药物今后的设计和筛选提供可靠的理论依据。
Tubulin is one of validated targets for development of anticancer drugs. CoMFA and CoMSIA were applied to systematic investigate 3D-QSAR of 53 Didehydropiperazine-2, 5-dione derivatives as potent antimicrotubule agents, and the 3D-QSAR models were builtcd. The coefficients of cross-validation q2 and non cross-validation r2 for CoMFA model were 0.642 and 0.996, for CoMSIA model were 0.724 and 0.908 respectively. The models had good predictive capability and stability. The contour maps provided useful guidance for more potent anticancer drugs discovery.
出处
《计算机与应用化学》
CAS
CSCD
北大核心
2014年第1期86-90,共5页
Computers and Applied Chemistry
基金
国家自然科学基金资助项目(31170747
81171508)
重庆巴南区科技计划专项项目(2012Q119)
