Molecular electrostatic potentials as input for the alignment of HIV-1 integrase inhibitors in 3D QSAR.
Comparative molecular similarity indices analysis (CoMSIA), a three-dimensional quantitative structure activity relationship (3D QSAR) paradigm, was used to examine the correlations between the calculated physicochemical properties and the in vitro activities (3'-processing and 3'-strand transfer inhibition) of a series of human immunodeficiency virus type 1 (HIV-1) integrase inhibitors. The training set consisted of 34 molecules from five structurally diverse classes: salicylpyrazolinones, dioxepinones, coumarins, quinones, and benzoic hydrazides. The data set was aligned using extrema of molecular electrostatic potentials (MEPs). The predictive ability of the resultant model was evaluated using a test set comprised of 7 molecules belonging to a different structural class of thiazepinediones. A CoMSIA model using an MEP-based alignment showed considerable internal as well external predictive ability (r2(cv) = 0.821, r2(pred) = 0.608 for 3'-processing; and r2(cv) = 0.759, r2(pred.) = 0.660 for 3'-strand transfer).
Makhija
M T
MT
Pharmaceutical Division, Department of Chemical Technology, University of Mumbai, Matunga, India.
Kulkarni
V M
VM
D003198:Computer Simulation; D015195:Drug Design; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity
D019428:HIV Integrase Inhibitors