In silico prediction of novel phosphodiesterase type-5 inhibitors derived from Sildenafil, Vardenafil and Tadalafil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)A series of drug-like compounds derived from Sildenafil, Vardenafil and Tadalafil analogues were modelled through the MIA-QSAR (multivariate image analysis applied to quantitative structure-activity relationships) ligand-based approach. A highly predictive model was achieved and novel compounds, miscellany of substructures of these three representative phosphodiesterase type-5 (PDE-5) inhibitors were predicted using the calibration parameters obtained through partial least squares (PLS) regression. The high bioactivities of eight promising compounds were corroborated by docking evaluation. Calculated ADME-Tox (absorption, distribution, metabolism, excretion and toxicity) profiles for such compounds suggest advantages of some of them over the currently available, most common drugs used for the treatment of erectile dysfunction. (C) 2008 Elsevier Ltd. All rights reserved.161675997606Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPEMIG [CEX 415/06, CEX 353/06, CEX 97/07]FAPESP [2005/59649-0