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 inhibitors that inhibit integrase mediated cleavage (3'-processing step) and integration (3'-strand transfer step) in vitro was performed. The training set consisted of 35 molecules from five structurally diverse classes: salicylhydrazines, lichen acids, coumarins, quinones, and thiazolothiazepines. Models derived using semiempirical (MOPAC AM1 and PM3) calculated normal-mode frequencies were compared. The predictive ability of each resultant model was evaluated using a test set comprised of six molecules belonging to a different structural class: hydrazides. Models derived using AM1 method showed considerable internal as well as external predictivity (r(2)(cv) = 0.806, r(2)(pred) = 0.761 for 3'-processing and r(2)(cv) = 0.677, r(2)(pred) = 0.591 for 3'-strand transfer).
Makhija
M T
MT
Pharmaceutical Division, Department of Chemical Technology, University of Mumbai, Matunga, Mumbai 400 019 India.
Kulkarni
V M
VM
D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000737:chemistry*; D016018:Least-Squares Analysis; D008968:Molecular Conformation
D019428:HIV Integrase Inhibitors; D019427:HIV Integrase