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Title

Pharmacophore elucidation and molecular docking studies on phosphodiesterase-5 inhibitors

 

Authors

Awwad Abdoh Radwan1, 2

 

Affiliation

1King Saud University, College of Pharmacy, Department of Pharmaceutics, Riyadh 11451, Saudi Arabia; 2Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt

 

Email

dhna_2001@hotmail.com

 

Article Type

Hypothesis

 

Date

Received December 21, 2014; Accepted January 10, 2015; Published February 28, 2015

 

Abstract

cGMP-binding cGMP-specific PDE, PDE5 plays a key role in the hydrolysis of cyclic guanidine monophosphate. Because cGMP mediates vascular functions, a PDE5 inhibitor that elevates cGMP level is an attractive means for vasodilatation and treatment of erectile dysfunction. In this paper we report the elucidation of the common pharmacophore hypothesis of different classes of PDE5 inhibitors. Using LigandScout program, pharmacophore modelling studies were performed on prior reported potent PDE5 inhibitors with a variety of scaffolds in order to identify one common set of critical chemical features of these PDE5 inhibitors 1-52. The best pharmacophore model, model-1, characterized by four chemical features: one aromatic ring, one hydrophobe, one hydrogen acceptors and one hydrogen donor. Using Dock6 program, docking studies were performed in order to investigate the mode of binding of these compounds. The molecular docking study allowed confirming the preferential binding mode of different classes of PDE5 inhibitors inside the active site. The obtained binding mode was as same as that of vardenafil, X-ray ligand with different orientation with varied PDE5 inhibitorsí scaffold.

 

Keywords

pharmacophore; molecular Docking; Phosphodiesterase-5

 

Citation

Radwan, Bioinformation 11(2): 063-066 (2015)
 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.