Pharmacophore and molecular docking based identification of novel structurally diverse PDE-5 inhibitors

In view that PDE5 is a potential target for the design of antihypertensive drugs a pharmacophore and molecular docking based virtual screening protocol was implemented. Two hydrophobic and one ring aromatic feature containing pharmacophore model was developed, validated, and used to mine Maybridge chemical compound database. This led to retrieval of many hits which were screened on the basis of estimated activity, fit value, and Lipinski’s violation. The eight selected hits were docked into the active site of PDE5 to evaluate the specific inhibitor-enzyme interactions finally leading to identification of two potent, druggable PDE5 inhibitors with good LibDock scores. Both the compounds showed interaction with Gln 817, Tyr 612, and Ala 767 amino acid residues testifying the results obtained from pharmacophore modeling.