新型Atorvastatin类HMGR抑制剂的3D-QSAR和分子对接  

3D-QSAR and Molecular Docking of Novel Atorvastatin Derivatives as HMGR Inhibitors

作　　者：王志[1] 蔡明峰 叶良春[1] 刘卓裕 程利平[1] 

机构地区：[1]上海应用技术学院化学与环境工程学院,上海201418

出　　处：《上海应用技术学院学报（自然科学版）》2015年第4期327-332,343,共7页Journal of Shanghai Institute of Technology: Natural Science

基　　金：上海市自然科学基金资助项目(15ZR1440400);上海市大学生科技创新创业资助项目(PE2014044;PE2014069);上海应用技术学院本科毕业设计重点资助项目(33110T145016)

摘　　要：羟甲基戊二酰辅酶A还原酶(HMGR)是内源性胆固醇合成的重要催化限速酶,通过抑制HMGR的活性可以降低内源性胆固醇的合成.HMGR抑制剂(他汀类)是治疗心血管疾病的最佳药物之一.运用计算机辅助药物设计(CADD)方法,综合三维定量构效关系(3D-QSAR)和分子对接分析研究已合成的HMGR抑制剂的结构与抑制活性之间的关系.根据最优3D-QSAR模型,再结合分子对接分析,设计出新型活性高的HMGR抑制剂分子.Hydroxymethylglutaric acyl coenzyme A reductase（HMGR）is an important catalytic ratelimiting enzyme for the synthesis of endogenous cholesterol.The synthesis of endogenous cholesterol can be reduced by inhibiting the activity of HMGR.HMGR inhibitors（statins）are one of the best drugs available for treating the cardiovascular diseases（CVD）.Combining three-dimensional quantitative structure-activity relationship（3D-QSAR）and molecular docking analysis and with the application of the computer aided drug design（CADD）,the relationship between the synthesized HMGR inhibitor structures and inhibitory activity was studied.On the basis of the optimal 3D-QSAR model and the integrated molecular docking,a new type of HMGR inhibitors molecule with higher activity was designed.

关 键 词：他汀类药物 三维定量构效关系 分子对接 羟甲基戊二酰辅酶A还原酶 

分 类 号：R914[医药卫生—药物化学]