In Vitro Experimental and Computational Studies of the Vasorelaxant Effects of Quinazolin-4(3H)-one and Its Interaction with α1-Adrenergic Receptors.

The problem of hypertension continues to be a major health challenge in the world, and the need to develop new and safer vasorelaxant agents continues to be a necessity. A compound with known pharmacological benefits that is yet to be examined for its role in blood pressure regulation, quinazolin-4(3H)-one, was synthesized and characterized, and then its vasorelaxant effects were investigated. In vitro vasorelaxation effects were evaluated on isolated rat aortic rings that had been pre-contracted with Epinephrine (EP) and Potassium chloride (KCl). An integrated in silico approach was employed to elucidate the compound's interactions and properties. The AutoDock Vina (Version 1.5.7) tool was used for molecular docking. Following rigorous protein and ligand preparation, key binding modes at the active sites of the alpha-1 adrenergic receptor (α1-AR) and L-type calcium channels were identified. Quantum chemical properties were calculated by Gaussian 09 using Density Functional Theory (DFT). A combination of the B3LYP functional and the 6-311G (d,p) basis set was used. Molecular Electrostatic Potential (MEP) analysis was performed using GaussView. ADME-Tox, bioavailability, and pharmacokinetic properties were predicted using SwissADME and pkCSM. Quinazolin-4(3H)-one produced concentration-dependent relaxation of EP-pre-contracted aortic rings, regardless of the presence of the endothelium. Moreover, the compound significantly and concentration-dependently inhibited sustained EP-induced contractions. These findings indicate an inhibitory effect on EP-induced vascular contraction, but do not establish a specific α1-adrenergic receptor-mediated mechanism. Molecular docking analysis suggested a favorable potential interaction of quinazolin-4(3H)-one with α1-AR, although this computational prediction does not confirm a functional receptor-mediated effect. DFT and MEP analyses indicated favorable electronic properties and charge distribution that may contribute to molecular interactions. In silico ADME-Tox evaluation predicted favorable drug-like properties, including oral bioavailability and good absorption, with no major toxicity alerts. Overall, quinazolin-4(3H)-one represents a promising lead compound for further investigation of its vasorelaxant and potential antihypertensive properties. Further pharmacological and in vivo studies are required to elucidate its precise mechanism of action and establish its safety and therapeutic potential.