CoMFA Model of Anti-tumor Activity for Fluoroquinolon-3-yl s-Triazole Sulfide-ketone Derivatives and Implications for Molecular Design  

作　　者：FENG Hui FENG Chang-Jun 冯惠;冯长君(School of Chemistry&Chemical Engineering,Xuzhou University of Technology,Xuzhou 221018,China)

机构地区：[1]School of Chemistry&Chemical Engineering,Xuzhou University of Technology,Xuzhou 221018,China

出　　处：《Chinese Journal of Structural Chemistry》2021年第6期703-710,683,共9页结构化学（英文）

基　　金：the National Natural Science Foundation of China(21075138);special fund of State Key Laboratory of Structural Chemistry(2016028)。

摘　　要：Comparative molecular field analysis(CoMFA)techniques were used to perform three-dimensional quantitative structure-activity relationship(3D-QSAR)studies on the anti-tumor activity(pIH and pIC)of 28 fluoroquinolon-3-yl s-triazole sulfide-ketone derivatives(FQTSDs)against two cancer cell lines,including human hepatoma Hep-3B cells and human pancreatic cancer Capan-1 cells.23 compounds were randomly selected as the training set to establish the prediction models,which were verified by the test set of 6 compounds containing template molecule.The obtained cross-validation(Rcv2)and non-cross-validation correlation coefficients(R2)of the CoMFA models were 0.477 and 0.850 for pIH,and 0.421 and 0.836 for pIC,respectively.The contributions of steric and electrostatic fields to pIH were determined to be 48.1%and 51.9%,and those to pIC were 49.4%and 50.6%,respectively.The CoMFA models were then used to predict the activities of the compounds in the training and testing sets,and the models had a strong stability and good predictability.Based on the 3D contour maps,four novel FQTSDs with a higher anti-tumor activity were designed.However,the effectiveness of these novel FQTSDs is still needed to be verified by experimental results.

关 键 词：fluoroquinolon-3-yl s-triazole sulfide-ketone derivative anti-tumor activity 3D-QSAR comparative molecular field analysis molecular design 

分 类 号：TQ460.1[化学工程—制药化工]