3D-QSAR CoMFA AND CoMSIA STUDIES ON A SET OF DIVERSE α1a-ADRENERGIC RECEPTOR ANTAGONISTS†

Abstract

The α-adrenergic receptors (α-ARs) modulate a number of intracellular processes and among these α1a- adrenergic receptors play an important role in the regulation of physiological processes related to cardiovascular system. In view of its therapeutic potential, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies were performed on a diverse set of α-adrenergic receptor antagonists to understand the structural factors affecting their antagonist activity. Both CoMFA (q2 = 0.709, r2 = 0.962, and r2 predictive = 0.629) and CoMSIA (q2 = 0.648, r2 = 0.949, and r2 predictive = 0.656) models gave statistical significant results. The generated CoMFA & CoMSIA models suggest that steric, electrostatic and hydrophobic interactions play an important role in describing the variation in antagonistic activity. The models may be useful in the identification and optimization of novel scaffolds with potent α1a –adrenergic receptor antagonistic activity.