Multivariate QSAR study of 4,5-dihydroxypyrimidine carboxamides as HIV-1 integrase inhibitors.
A multivariate QSAR study of thirty-three 4,5-dihydroxypyrimidine carboxamides as HIV-1 integrase (HIV-1 IN) inhibitors was performed employing Ordered Predictors Selection (OPS) algorithm and PLS regression for variable selection and model construction, respectively. Four descriptors were chosen and a reasonable model (n=30; R(2)=0.68; SEC=0.57; PRESS(cal)=8.72; F((2,27))=28.97; Q(2)(LOO)=0.58; SEV=0.62; PRESS(val)=11.62; R(2)(pred)=0.87; SEP=0.29; ARE(pred)=4.37%; k=0.99; k'=1.01; |r(2)(0)-r(2)(0)'|=-0.18) was built with two latent variables (59.54% of the information). Leave-N-out (LNO) and Y-randomization methods confirmed the model robustness. The descriptors indicated that the HIV-1 IN inhibition depends on the electronic distribution of the investigated compounds. The interpretation of the model is related to the most accepted mechanism of action.
de Melo
Eduardo Borges
EB
Centro de Ciências Médicas e Farmacêuticas, Universidade Estadual do Oeste do Paraná, Rua Universitária 2069, 85819-110 Cascavel, PR, Brazil. ebmelo@unioeste.br
Ferreira
Márcia Miguel Castro
MM