A three-dimensional quantitative structure-activity relationship （3D-QSAR） study of a series of 7,8-dialkyl-l,3-diaminopyrrolo-[3,2-f] quinazolines with anticancer activity as dihydrofo- late reductase （DHFR） inhibitors was carried out by using the comparative molecular field analysis （CoMFA）, on the basis of our reported 2D-QSAR of these compounds. The es- tablished 3D-QSAR model has good quality of statistics and good prediction ability; the non cross-validation correlation coefficient and the cross-validation value of this model are 0.993 and 0.619, respectively, the F value is 193.4, and the standard deviation SD is 0.208. This model indicates that the steric field factor plays a much more important role than the electrostatic one, in satisfying agreement with the published 2D-QSAR model. However, the 3D-QSAR model offers visual images of the steric field and the electrostatic field. The 3D-QSAR study further suggests the following： to improve the activity, the substituent R^1 should be selected to be a group with an adaptive bulk like Et or i-Pr, and the substituent R should be selected to be a larger alkyl. In particular, based on our present 3D-QSAR as well as the published 2D-QSAR, the experimentMly-proposed hydrophobic binding mechanism on the receptor-binding site of the DHFR can be further explained in theory. Therefore, the QSAR studies help to further understand the ＂hydrophobic binding＂ action mechanism of this kind of compounds, and to direct the molecular design of new drugs with higher activity.
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,
Three-dimensional quantitative structure activity relationship （3D-QSAR） and docking studies of a series of arylthioindole derivatives as tubulin inhibitors against human breast cancer cell line MCF-7 have been carried out. An optimal 3D-QSAR model from the comparative molecular field analysis （CoMFA） for training set with significant statistical quality （R2=0.898） and predictive ability （q2=0.654） was established. The same model was further applied to predict pIC50 values of the compounds in test set, and the resulting predictive correlation coefficient R2（pred） reaches 0.816, further showing that this CoMFA model has high predictive ability. Moreover, the appropriate binding orientations and conformations of these compounds interacting with tubulin are located by docking study, and it is very interesting to find the consistency between the CoMFA field distribution and the 3D topology structure of active site of tubulin. Based on CoMFA along with docking results, some important factors improving the activities of these compounds were discussed in detail and were summarized as follows： the substituents R3-R5 （on the phenyl ring） with higher electronegativity, the substituent R6 with higher eleetropositivity and bigger bulk, the substituent R7 with smaller bulk, and so on. In addition, five new compounds with higher activities have been designed. Such results can offer useful theoretical references for experimental works.
Three-dimensional quantitative structure-activity relationship(3D-QSAR) and docking studies were performed on ...
Wen Juan Wua,b,Rong Zhanga,Yong Shenb,Kang-Cheng Zhengb~* a Department of Physical Chemistry,Guangdong Pharmaceutical University,Guangzhou,510006, b School of Chemistry and Chemical Engineering,Sun Yat-Sen University,Guangzhou,510275,
＜正＞Currently,inhibition of the activator protein-1（AP-1） and nuclear factor kappa B （NF-κB） transcriptional ac...
Li Qian~(a,b),Shi-Wen Huang~a,Suo-Yi Huang~a,Yong Shen~b,Kang-Cheng Zheng~(b*) Department of Chemistry,Youjiang Medical College for Nationalities,Guangxi,Baise,533000,China. School of Chemistry and Chemical Engineering,Sun Yat-Sen University,Guangzhou,510275,China.
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.
