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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Antunes, Joao E. [1] ; Freitas, Matheus P. [1] ; da Cunha, Elaine F. F. [1] ; Ramalho, Teodorico C. [1] ; Rittner, Roberto [2]
Total Authors: 5
Affiliation:
[1] Univ Fed Lavras UFLA, Dept Quim, BR-37200000 Lavras, MG - Brazil
[2] Univ Estadual Campinas, Inst Chem, BR-13084971 Campinas, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Bioorganic & Medicinal Chemistry; v. 16, n. 16, p. 7599-7606, AUG 15 2008.
Web of Science Citations: 25
Abstract

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)

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