Potential virtual lead identification in the discovery of renin inhibitors: Application of ligand and structure-based pharmacophore modeling approaches

Renin, an enzyme by cleaving angiotensinogen to angiotensin-I, controls the first and rate-limiting step of renin-angiotensin system that is associated with blood pressure. Thus Ligand and structure-based pharmacophore models were developed in this study to identify new potential leads inhibiting this rate-limiting enzyme as an efficient way to treat blood pressure. X-ray predicted binding modes of most active compounds were used in ligand-based approach whereas the 3D structural information of renin was used in structure-based approach. Pharmacophore models were validated using various methods and utilized in database searching to identify potential hits. Drug-like filters and molecular docking studies led us identifying the final hits to be employed in designing new class of future renin inhibitors. (C) 2011 Elsevier Masson SAS. All rights reserved.