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

Autor(es)

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

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 44, n. 9, p. 3577-3583, SEP 2009.
• Citações Web of Science: 30

Resumo

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)

• Processo FAPESP: 04/04686-5 - Abordagens quimiométricas clássicas e novas em estudos teóricos de substâncias bioativas
• Beneficiário: Marcia Miguel Castro Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático