Background: This research centers on the development and spectroscopic characterization of new quinazolin-4(3H)-one-isoxazole derivatives (5a–e). The aim was to investigate the regioselectivity of the 1,3-dipolar cycloaddition involving arylnitriloxides and N-propargylquinazolin-4(3H)-one, and to assess the antioxidant properties of the synthesized compounds. The synthetic approach started with the alkylation of quinazolin-4(3H)-one using propargyl bromide, followed by a 1,3-dipolar cycloaddition reaction. Methods: The structural identification of the products was performed using various spectroscopic methods, such as IR, 1H, 13C, and HMBC NMR, HRMS, and single-crystal X-ray diffraction. To further examine the regioselectivity of the cycloaddition, Density Functional Theory (DFT) calculations at the B3LYP/6-31G(d) level were employed. Additionally, the antioxidant potential of the compounds was tested in vitro using DPPH (2,2-Diphenyl-1-picrylhydrazyl)radical scavenging assays. The reaction selectively produced 3,5-disubstituted isoxazoles, with the regiochemical outcome being independent of the substituents on the phenyl ring. Results: Theoretical calculations using DFT were in agreement with the experimental results, revealing activation energies of −81.15 kcal/mol for P-1 and −77.32 kcal/mol for P-2, favoring the formation of P-1. An analysis of the Intrinsic Reaction Coordinate (IRC) confirmed that the reaction proceeded via a concerted but asynchronous mechanism. The antioxidant tests demonstrated that the synthesized compounds exhibited significant radical scavenging activity, as shown in the DPPH assay. The 1,3-dipolar cycloaddition of arylnitriloxides with N-propargylquinazolin-4(3H)-one successfully resulted in novel 3,5-disubstituted isoxazoles. Conclusions: The experimental findings were well-supported by theoretical predictions, and the antioxidant assays revealed strong activity, indicating the potential for future biological applications of these compounds.

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.

This study reports the synthesis of spiro-lactam hydrazones catalysed by Moroccan Es-sifa natural clay, with structural characterization, in silico studies and evaluation of biological activities.

This article reports the synthesis of novel xanthene-hydrazone derivatives, their structural characterization, and the evaluation of their vasorelaxant properties using both in vitro and in silico approaches.

A novel O -allylated fluorescein hydrazone derivative was synthesized from fluorescein through a three-step synthetic route.