Synthesis and Anti-Diabetic Evaluation of 2-Phenyl-3H-quinazolin-4-one Derivatives

Background/Objectives: Diabetes mellitus is a common endocrine disorder characterized by hyperglycemia, which is increasing steadily all over the world. Current medications are limited due to lower efficacy and side effects; therefore, the introduction of novel compounds is crucial to improve therapeutic outcomes for diabetic patients. The objective of this study was to synthesize and evaluate 2-phenyl-3H-quinazolin-4-one and its derivatives for the glucose uptake across the yeast cell membranes, alpha-amylase inhibition, and alpha-glucosidase inhibition in silico and in vitro. Methods: The synthesis of 2-phenyl-3H-quinazolin-4-one and its derivatives was carried out by oxidative cyclocondensation of 2-aminobenzamide (anthranilamide) with various benzaldehydes in the presence of aqueous iron (III) chloride. The synthesized compounds were characterized by melting point determination and spectroscopic techniques, including FTIR, NMR and HRMS. Results: In the glucose uptake by yeast assay, compound 3f had a lower 50% glucose uptake value of 24.02 ± 0.96 mM, compared with the standard drug metformin (25.99 ± 2.41 mM). The alpha-amylase inhibition bioassay showed that compound 3e exhibited very potent inhibition, with an IC50 of 0.43 ± 0.05 mM, compared with the standard drug acarbose (0.53 ± 0.21 mM). Compound 3l exhibited strong alpha-glucosidase inhibition, with an IC50 of 0.42 ± 0.10 mM, compared with the standard drug acarbose (0.29 ± 0.50 mM). Coclusions: These findings suggest the potential of synthesized 2-phenyl-3H-quinazolin-4-one derivatives, 3a–o, as promising candidates for managing diabetes mellitus. However, further studies are required to validate their efficacy and determine their mechanisms of action.