Quantitative structure-activity relationship studies of diarylpyrimidine derivatives as anti-HIV drugs using new three-dimensional structure descriptors

摘要

A novel three-dimensional holographic vector of atomic interaction field (3D-HoVAIF) was used to describe the chemical structures of 34 wild-type DAPYs, 33 mutant form L100I, 30 mutant form Y181C and 29 mutant form Y188L as anti-HIV drugs. Here four quantitative structure activity relationship models were built by partial least square regression. The estimation stability and prediction ability of models were strictly analyzed by both internal and external validations. The correlation coefficient (R_(cum)~2, leave-one-out cross-validation correlation coefficient (Q_(CV)~2) and predicted values versus experimental ones of external samples (Q_(ext)~2) were 0.925, 0.769 and 0.949 for 34 diarylpyrimidines; 0.899, 0.788 and 0.889 for 33 mutant form L100I; 0.844, 0.761 and 0.935 for 30 mutant form Y181C; 0.890, 0.757 and 0.912 for 29 mutant form Y188L. These values indicated that the built PLS models had both favorable estimation stability and good prediction capabilities. Furthermore, the satisfactory results showed that 3D-HoVAIF could preferably express the information related to the biological activity of DAPY derivatives.