3D QSAR Study of Simultaneous AT1 and ETA Antagonists as Anti- hypertensive Drugs

Both Angiotensin (AT1) and Endothelin (ETA) antagonists cause lower blood pressure in hypertensive patients. A compound with dual AT1 and ETA receptors antagonistic function may be more efficacious antihypertensive drug. In order to understand the most important structural characteristics of AT1 and ETA inhibitors and the correlation of these features their potency, a Molecular Interaction Fields (MIF) based alignment independent three-dimensional quantitative structure-activity relationship (3D-QSAR) study was conducted. The resulted PLS model analysis indicated that the computed activities were in excellent agreement with experimentally observed values, for AT1 (R2= 0.89,Q2LOO= 0.83 and R2pred= 0.873) and for ETA ( R2= 0.82, Q2LOO= 0.64 and R2pred= 0.778). Finally, the inhibitory activity of each AT1 and ETA inhibitor groups were predicted using the other receptor validated QSAR model and the most potent ones were selected for further studies