A QSAR study and molecular design of benzothiazole derivatives as potent anticancer agents  

作　　者：CHEN JinCan QIAN Li SHEN Yong CHEN LanMei ZHENG KangCheng 

机构地区：[1]School of Chemistry and Chemical Engineering,Zhongshan(Sun Yat-Sen)University,Guangzhou 510275,China

出　　处：《Science China Chemistry》2008年第2期111-119,共9页中国科学（化学英文版）

基　　金：the National Natural Science Foundation of China (Grant No. 20673148);the Natural Science Foundation of Guangdong Province of China (Grant No. 05003264)

摘　　要：A quantitative structure-activity relationship (QSAR) of a series of benzothiazole derivatives showing a potent and selective cytotoxicity against a tumorigenic cell line has been studied by using the density functional theory (DFT), molecular mechanics (MM+) and statistical methods, and the QSAR equation was established via a correlation analysis and a stepwise regression analysis. A new scheme determining outliers by “leave-one-out” (LOO) cross-validation coefficient (q n-i 2 ) was suggested and successfully used. In the established optimal equation (excluding two outliers), the steric parameter (MR R) and the net charge (Q FR) of the first atom of the substituent (R), as well as the square of hydrophobic parameter (IgP)2 of the whole molecule, are the main independent factors contributing to the anticancer activities of the compounds. The fitting correlation coefficient (R 2) and the cross-validation coefficient (q 2) values are 0.883 and 0.797, respectively. it indicates that this model has a significantly statistical quality and an excellent prediction ability. Based on the QSAR studies, 4 new compounds with high predicted anticancer activities have been theoretically designed and they are expected to be confirmed experimentally.A quantitative structure-activity relationship (QSAR) of a series of benzothiazole derivatives showing a potent and selective cytotoxicity against a tumorigenic cell line has been studied by using the density functional theory (DFT), molecular mechanics (MM+) and statistical methods, and the QSAR equation was established via a correlation analysis and a stepwise regression analysis. A new scheme determining outliers by "leave-one-out" (LOO) cross-validation coefficient (q2n-i) was suggested and successfully used. In the established optimal equation (excluding two outliers), the steric parameter (MRR) and the net charge (QFR) of the first atom of the substituent (R), as well as the square of hydrophobic parameter (lgP)2 of the whole molecule, are the main independent factors contributing to the anticancer activities of the compounds. The fitting correlation coefficient (R2) and the cross-validation coefficient (q2) values are 0.883 and 0.797, respectively. It indicates that this model has a significantly statistical quality and an excellent prediction ability. Based on the QSAR studies, 4 new compounds with high predicted anticancer activities have been theoretically designed and they are expected to be confirmed experimentally.

关 键 词：QSAR ANTICANCER activity BENZOTHIAZOLE DERIVATIVE DFT polarity interference 

分 类 号：R914[医药卫生—药物化学]