Eigen value analysis of HIV-1 integrase inhibitors

A three-dimensional quantitative structure activity relationship using the eigen value analysis (EVA) paradigm applied to 41 HIV-1 integrase inhibitor s that inhibit integrase mediated cleavage (3'-processing step) and integra tion (3'-strand transfer step) in vitro was performed. The training set con sisted of 35 molecules from five structurally diverse classes: salicylhydra zines, lichen acids, coumarins, quinones, and thiazolothiazepines. Models d erived using, semiempirical (MOPAC AM1 and PM3) calculated normal-mode freq uencies were compared. The predictive ability of each resultant model was e valuated using a test set comprised of six molecules belonging to a differe nt structural class: hydrazides. Models derived using AM1 method showed con siderable internal as well as external predictivity (r(cv)(2) = 0.806, r(pr ed)2 = 0.761 for 3'-processing and r(cv)(2) = 0.677, r(pred)(2) = 0.591 for 3'-strand transfer).