GPR35受体香豆素类激动剂三维定量构效关系研究  

Three-Dimensional Quantitative Structure-Activity Relationship Studies on Coumarins as Agonists of G Protein-Coupled Receptor 35

作　　者：任聪 于大永[1] 魏来[2] 张秀莉 冯宝民[1] 史丽颖[1] 曹洪玉[1] REN Cong;YU Da-yong;WEI Lai;ZHANG Xiu-li;FENG Bao-min;SHI Li-ying;CAO Hong-yu(College of Life Science and Technology,Dalian University,Dalian,116622,China;Dalian Institute of Physical Chemistry,Chinese Academy of Sciences,Dalian,116023,China)

机构地区：[1]大连大学生命科学与技术学院,大连116622 [2]中国科学院大连物理化学研究所,大连116023

出　　处：《天然产物研究与开发》2018年第6期1066-1072,共7页Natural Product Research and Development

基　　金：国家自然科学基金(31270398);国家自然科学基金青年(21601025);辽宁省自然科学基金(201602027);国家大学生创新计划(201711258000012)

摘　　要：本实验采用比较分子力场分析法(Co MFA)和比较分子相似性指数分析法(Co MSIA)建立GPR35受体香豆素类激动活性的三维定量构效关系(3D-QSAR)模型,以确定该类激动剂的分子结构与其生物活性之间的定量关系。在预测半数有效浓度(EC_(50))的Co MFA模型中,训练集抽一法(LOO)交叉验证系数q^2=0.559,非交叉验证系数r^2=0.887,标准偏差SE=0.382;在Co MSIA模型中,训练集抽一法交叉验证系数q^2=0.627,非交叉验证系数r^2=0.915,标准偏差SE=0.365。在预测半数抑制浓度(IC_(50))的Co MFA模型中,训练集抽一法交叉验证系数q^2=0.600,非交叉验证系数r^2=0.903,标准偏差SE=0.375;在Co MSIA模型中,训练集抽一法交叉验证系数q^2=0.566,非交叉验证系数r^2=0.914,标准偏差SE=0.378。EC_(50)和IC_(50)的两个3D-QSAR模型预测结果同实验数据基本一致,说明模型的预测能力较好。本实验根据模型预测结果,对配体分子的结构进行分析,为获得具有更高活性的配体分子提供理论依据。In this study,a three-dimensional quantitative structure-activity relationship（ 3 D-QSAR） model of GPR35 receptor agonists was established by comparative molecular field analysis（ Co MFA） and comparative molecular similarity indices analysis（ Co MSIA）,the quantitative relationship between the structure of the agonists and its biological activities was determined. In the Co MFA model,which was employed to calculate the half effective concentration,the final LOO（ Leave-one-out） cross-validation coefficient（ q2） is 0. 559,the non-cross validation coefficient（ r2） is 0. 887,standard deviation（ SE） is 0. 382,and in the Co MSIA model,the final decision coefficient（ q2） is 0. 627,non-cross validation coefficient（ r2） is 0. 915,and standard deviation（ SE） is 0. 365. In the Co MFA model,which was employed to calculate the half inhibitory concentration,the final LOO（ Leave-one-out） cross-validation coefficient（ q2） is 0. 600,non-cross validation coefficient（ r2） is 0. 903,standard deviation（ SE） is 0. 375,and in the Co MSIA model,the final decision coefficient（ q2） is 0. 566,non-cross validation coefficient（ r2） is 0. 914,and standard deviation（ SE） is0. 378. One satisfactory 3D-QSAR model possessing predictive capability was obtained,EC50 and IC50 values which predicted by 3D-QSAR model are almost same with experimental data. In this experiment,according to the predicted results,the structures of the ligand molecules were analyzed. The 3D-QSAR model can be applied to design new coumarin derivatives potent GPR35 agonists.

关 键 词：GPR35受体 香豆素类化合物 三维定量构效关系 比较分子力场分析法 比较分子相似性指数分析法 

分 类 号：R914.2[医药卫生—药物化学]