de Melo E. B., Ferreira M. M. C., "Multivariate QSAR study of 4,5-dihydroxypyrimidine
carboxamides as HIV-1 integrase inhibitors",
Eur. J. Med. Chem.,
44(9),
3577-3583 (Sep 2009).
[Article]
Abstract.
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; R2
= 0.68; SEC = 0.57; PRESScal = 8.72; F(2,27)
= 28.97; Q2LOO = 0.58;
SEV = 0.62; PRESSval = 11.62; R2pred
= 0.87; SEP = 0.29; AREpred = 4.37%; k
= 0.99; k' = 1.01; |r20
- r20'| = -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.
Keywords.
QSAR; 4,5-Dihydroxypyrimidine Carboxamides; HIV-1 Integrase; OPS; PLS.
Keywords Plus.