3D-QSAR CoMFA and CoMSIA studies on a set of diverse α_1a-adrenergic receptor antagonists

摘要

The α-adrenergic receptors (α-ARs) modulate a number of intracellular processes and among these α_1a-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 set of diverse α-AR antagonists to understand the structural factors affecting their antagonistic activity where both CoMFA (q _train2 = 0.709, r _train2 = 0.962, and r _predictive2 = 0.629) and CoMSIA (q _train2 = 0.648, r _train2 = 0.949, and r _predictive2 = 0.656) models gave statistical significant results. The generated CoMFA and CoMSIA models suggest that steric, electrostatic and hydrophobic interactions play an important role in describing the variation in antagonistic activity. Therefore, the models may be useful in the identification and optimization of novel scaffolds with potent α_1a-adrenergic receptor antagonistic activity.