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

Autor(es)

Antunes, Joao E. ^[1] ; Freitas, Matheus P. ^[1] ; da Cunha, Elaine F. F. ^[1] ; Ramalho, Teodorico C. ^[1] ; Rittner, Roberto ^[2]

Afiliação do(s) autor(es)

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

^[2] Univ Estadual Campinas, Inst Chem, BR-13084971 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Bioorganic & Medicinal Chemistry; v. 16, n. 16, p. 7599-7606, AUG 15 2008.
• Citações Web of Science: 25

Resumo

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. (AU)

• Processo FAPESP: 05/59649-0 - Estudos de estrutura eletrônica e molecular através de métodos espectroscópicos e cálculos teóricos
• Beneficiário: Roberto Rittner Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático