Bioactivities of a series of phosphodiesterase type 5 (PDE-5) inhibitors as modelled by MIA-QSAR

Author(s)

Antunes, Joao E. ^[1] ; Freitas, Matheus P. ^[1] ; Rittner, Roberto ^[2]

Affiliation

^[1] Univ Fed Lavras UFLA, Dept Quim, BR-37200000 Lavras, MG - Brazil

^[2] Univ Estadual Campinas, Phys Organ Chem Lab, Inst Chem, BR-13083971 Campinas, SP - Brazil

• Document type: Journal article
• Source: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 43, n. 8, p. 1632-1638, AUG 2008.
• Web of Science Citations: 18

Abstract

A series of cyclic guanine derivatives, phosphodiesterase type 5 (PDE-5) inhibitors, have been modelled using an image-based approach for quantitative structure-activity relationships (MIA-QSAR). The calibration model showed to be robust with a R(2) of 0.864 using five PLS components. The predictive ability of the model was tested through leave-one-out cross-validation, giving a Q(CV)(8) of 0.605 (Q(CV)(8) improves to 0.721 after removing two outliers). An external validation set was also used to give an account for the modelling capability, and the results agreed with the ones obtained from a 3D methodology previously applied to this series of compounds. The method showed to be a potential tool for predicting new drug-like compounds, as exemplified by calculating the activities of two new proposed congeners derived from the training set. (c) 2007 Elsevier Masson SAS. All rights reserved. (AU)

• FAPESP's process: 05/59649-0 - Conformational equilibria studies by nuclear magnetic resonance spectroscopy, infrared spectroscopy and theoretical calculations
• Grantee: Roberto Rittner Neto
• Support Opportunities: Research Projects - Thematic Grants