物理化学学报Issue(2)：431-438,8.DOI:10.3866/PKU.WHXB201211151
五元杂环并嘧啶类胸苷酸合成酶抑制剂的构效关系和分子对接
QSAR and Molecular Docking on Five-Membered Heterocyclopyrimidines as Thymidylate Synthase Inhibitors
摘要
Abstract
The three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for 38 five-membered heterocyclopyrimidine thymidylate synthase inhibitors by using comparative molecular field analysis (CoMFA) and comparative similarity indices analysis (CoMSIA) techniques. With the CoMFA model, the cross-validated value (q2) was 0.662, the non-cross-validated value (R2) was 0.921, and the external cross-validated value (Q2ext) was 0.85. And with the CoMSIA model, the corresponding q2, R2, and Q2ext values were 0.672, 0.884, and 0.81, respectively. The mode of action obtained by molecular docking was in agreement with the 3D-QSAR results. The results revealed that both models have good predictive capability to guide the design and structural modification of homologic compounds. Furthermore, these results also establish a base level for further research and development of new thymidylate synthase inhibitors.关键词
五元芳杂环并嘧啶衍生物/三维定量构效关系/比较分子场分析法/比较分子相似性指数分析法/分子对接Key words
Five-membered heterocyclopyrimidine derivative/Three dimensional quantitative structure-activity relationship/Comparative molecular field analysis/Comparative molecular similarity indices analysis/Molecular docking分类
化学化工引用本文复制引用
康从民,赵绪浩,王新宇,程家高,吕英涛..五元杂环并嘧啶类胸苷酸合成酶抑制剂的构效关系和分子对接[J].物理化学学报,2013,(2):431-438,8.基金项目
The project was supported by the National Natural Science Foundation of China (21072111,21172070,21272131) and Shandong Provincial Natural Science Foundation, China (ZR2011BM015).@@@@国家自然科学基金(21072111,21172070,21272131)和山东省自然科学基金(ZR2011BM015)资助项目 （21072111,21172070,21272131）
