Synthesis, In Silico, and In Vitro Evaluation of the Potential Antioxidant Activity of New Quinazoline Derivatives

Objective: This research aims to synthesize and characterize a new series of bioactive quinazoline derivatives, including Schiff bases, biquinazolinone, and benzothiazine, and to evaluate their bioactivity as antioxidants through both in silico and in vitro investigations. Methods: The new derivatives were synthesized with high yields by reacting Schiff base derivatives of quinazoline with 2-aminobenzoic acid and 2-mercaptobenzoic acid. The characterization of the prepared derivatives was carried out using FTIR, ¹H NMR, and ¹³C NMR techniques. In silico investigations included assessing pharmacokinetic and pharmacodynamic properties through the SwissADME online server and conducting molecular docking studies with the tyrosinase enzyme. In vitro assessments involved evaluating antioxidant activity using the total antioxidant capacity method and the DPPH scavenging activity method. Results and Discussion: In silico analysis revealed favorable pharmacokinetic and pharmacodynamic properties for all compounds. Compounds (III) and (IV) exhibited acceptable pharmacological characteristics. Molecular docking studies showed good docking scores for all compounds with the tyrosinase enzyme. In vitro assessments demonstrated noteworthy to excellent antioxidant activity for all compounds, with compounds (III) and (IV) exhibiting very strong activity compared to the standard reference, ascorbic acid. Conclusions: The synthesized quinazoline derivatives exhibit promising bioactivity as antioxidants, supported by both computational and experimental assessments. These findings suggest their potential for further exploration in the development of antioxidant agents, with particular emphasis on the notable performance of compounds (III) and (IV).