The interactions of Ru(Ⅱ) polypyridyl-type complexes with DNA have attracted considerable attention since the ...
Jun Lia,Ti Fang Miaob,Kang-Cheng Zheng~*b,and Liang-Nian Jib~(13) a Department of Chemistry,Guangdong Institute of Education,Guangzhou,510303,b School of Chemistry and Chemical Engineering,Sun Yat-Sen University,Guangzhou,510275,
The quantitative structure-activity relationship （QSAR） studies on a series of 7,8-dialkyl-1,3-diaminopyrrolo-[3,2-f]quinazolines, dihydrofolate reductase （DHFR） inhibitors as potential anticancer agents, have been carried out by using the density functional theory （DFT） method, molecular mechanics method （MM＋） and statistical method. Some QSAR models based on their lipophilic and steric parameters were built up via a stepwise regression analysis. It is very interesting to find that the established optimal QSAR equation involves only two descriptors： lipophilicity indexes Clog P and Clog P^2 However, such descriptors can quite well describe a significant statistic quality and have a remarkable predictive activity according to the square of adjusted correlation coefficient （RA^2 = 0.937） and the square of cross-validation coefficient （q^2=0.911） of this equation. The results show that the lipophilicity is a main factor affecting the anticancer activity of this series of antimetastatic agents, and the obtained equation describes a parabolic correlation between pIC50 and Clog P, and indicates a suitable range of Clog P （around 4.43） being very important for optimal pIC50 values. These QSAR studies can offer some useful references for understanding the action mechanism and performing the molecular design or modification of this series of antimetastatic agents.
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.
