Molecular modeling, quantum polarized ligand docking and structure-based 3D-QSAR analysis of the imidazole series as dual AT(1) and ET(A) receptor antagonists.

ABSTRACT:

Aim

Both endothelin ETA receptor antagonists and angiotensin AT1 receptor antagonists lower blood pressure in hypertensive patients. A dual AT1 and ETA receptor antagonist may be more efficacious antihypertensive drug. In this study we identified the mode and mechanism of binding of imidazole series of compounds as dual AT1 and ETA receptor antagonists.

Methods

Molecular modeling approach combining quantum-polarized ligand docking (QPLD), MM/GBSA free-energy calculation and 3D-QSAR analysis was used to evaluate 24 compounds as dual AT1 and ETA receptor antagonists and to reveal their binding modes and structural basis of the inhibitory activity. Pharmacophore-based virtual screening and docking studies were performed to identify more potent dual antagonists.

Results

3

SUBMITTER: Singh KD 

PROVIDER: S-EPMC4002566 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature