QSAR analysis of substituted benzylamino- and heterocyclylmethylamino-carbodithioate derivatives of 4-(3H)-quinazolinone using CoMFA and SCORE2.0  

作　　者：LIU Feng LIU ShiYing LIU Yan HAN DaXiong JIANG YuYang CAO ShengLi ZHAO YuFen 

机构地区：[1]Key Laboratory of Chemical Biology, Guangdong Province, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China [2]Key Laboratory of Bioorganic Phosphorus Chemistry, Ministry of Education, Department of Chemistry, School of Life Science and Engineering, Tsinghua University, Beijing 100084, China [3]Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry, Xiamen University, Xiamen 361005, China [4]Department of Chemistry, Capital Normal University, Beijing 100037, China

出　　处：《Chinese Science Bulletin》2007年第23期3200-3206,共7页

基　　金：Supported by the National Natural Science Foundation of China (Grant No. 20572060);Guangdong Fundamental Research Foundation of China (Grant No. 2005CCAO3400)

摘　　要：Thymidylate synthase (TS) is a critical enzyme for DNA biosynthesis and many nonclassical lipophilic antifolates targeting this enzyme are quite efficient and encouraging as antitumor drugs. In this paper, the binding model of 14 antifolates of substituted benzylamino- and heterocyclylmethylamino- carbodithioate derivatives of 4-(3H)-quinazolinone with TS is examined using molecular simulation methods―― FlexiDock and SCORE2.0. The resulting conformation and orientation of these antifolates are directly applied to CoMFA study. The robust QSAR model, its three-dimensional contour map, and binding score of these antifolates derived from SCORE2.0 provide guidelines for structural optimiza- tion of current antifolates. The experiment indicates that deletion of cancer chemopreventive structure of dithiocarbamate is unfavorable for interaction between TS and antifolates.Thymidylate synthase （TS） is a critical enzyme for DNA biosynthesis and many nonclassical lipophilic antifolates targeting this enzyme are quite efficient and encouraging as antitumor drugs. In this paper, the binding model of 14 antifolates of substituted benzylamino-and heterocyclylmethylamino-carbodithioate derivatives of 4-（3H）-quinazolinone with TS is examined using molecular simulation methods-FlexiDock and SCORE2.0. The resulting conformation and orientation of these antifolates are directly applied to CoMFA study. The robust QSAR model, its three-dimensional contour map, and binding score of these antifolates derived from SCORE2.0 provide guidelines for structural optimization of current antifolates. The experiment indicates that deletion of cancer chemopreventive structure of dithiocarbamate is unfavorable for interaction between TS and antifolates.

关 键 词：抗叶酸物 甲氨基 合酶 化学 

分 类 号：O6[理学—化学]