Pharmacophore elucidation and molecular docking studies on phosphodiesterase-5 inhibitors

cGMP-binding cGMP-specific PDE, PDE5 plays a key role in the hydrolysis of cyclic guanidine monophosphate. Because cGMPmediates vascular functions, a PDE5 inhibitor that elevates cGMP level is an attractive means for vasodilatation and treatment oferectile dysfunction. In this paper we report the elucidation of the common pharmacophore hypothesis of different classes of PDE5inhibitors. Using LigandScout program, pharmacophore modelling studies were performed on prior reported potent PDE5inhibitors 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, onehydrogen acceptors and one hydrogen donor. Using Dock6 program, docking studies were performed in order to investigate themode of binding of these compounds. The molecular docking study allowed confirming the preferential binding mode of differentclasses of PDE5 inhibitors inside the active site. The obtained binding mode was as same as that of vardenafil, X-ray ligand withdifferent orientation with varied PDE5 inhibitors׳ scaffold.