Multivariate QSAR study of 4,5-dihydroxypyrimidine carboxamides as HIV-1 integrase inhibitors

Author(s)

de Melo, Eduardo Borges ^{[1, 2]} ; Castro Ferreira, Marcia Miguel ^[1]

Affiliation

^[1] Univ Estadual Campinas, Dept Quim Fis, Inst Quim, Lab Quimiometria Teor & Aplicada, Campinas, SP - Brazil

^[2] Univ Estadual Oeste Parana, Ctr Ciencias Med & Farmaceut, Curso Farm, BR-85819110 Cascavel, PR - Brazil

• Document type: Journal article
• Source: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 44, n. 9, p. 3577-3583, SEP 2009.
• Web of Science Citations: 30

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; R(2)=0.68; SEC=0.57; PRESS(cal)=8.72; F((2.27))=28.97; Q(LOO)(2)=0.58; SEV = 0.62; PRESS(val) = 11.62; R(pred)(2) = 0.87; SEP = 0.29; ARE(pred) = 4.37%; k = 0.99; k' = 1.01; vertical bar r(0)(2) - r(0)(2)o'vertical bar = -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. (C) 2009 Elsevier Masson SAS. All rights reserved. (AU)

• FAPESP's process: 04/04686-5 - Classic and new chemiometric approaches in theoretic studies of bioactive substances
• Grantee: Marcia Miguel Castro Ferreira
• Support Opportunities: Research Projects - Thematic Grants