title: Potential virtual lead identification in the discovery of renin inhibitors: application of ligand and structure-based pharmacophore modeling approaches.
abstract: 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.
authors.affiliation: Division of Applied Life Science, BK21 Program, Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Gyeongsang National University (GNU), 900 Gazwa-dong, Jinju 660-701, Republic of Korea.
authors.forename: Sundarapandian
authors.initials: S
authors.lastname: Thangapandian
authors.forename: Shalini
authors.initials: S
authors.lastname: John
authors.forename: Sugunadevi
authors.initials: S
authors.lastname: Sakkiah
authors.forename: Keun Woo
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D012083:Renin / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D008024:Ligands; D012083:Renin; D000092502:Renin Inhibitors