Introduction: Heterocyclic compounds, such as quinazoline derivatives, have emerged as a promising class of compounds with notable antioxidant properties, which are crucial for mitigating oxidative stress associated with various diseases. Objective: This study focuses on the design, synthesis, and pharmacological evaluation of novel quinazoline derivatives aimed at enhancing their antioxidant activity. The design phase involved modifying the quinazoline core structure to incorporate functional groups that could improve electron-donating capabilities and metal-chelating properties. Materials and Methods: ADME studies and docking studies were performed with PDB ID: IYCI. The hydroxyl derivative of acetophenone was synthesised using an acylation reaction. From acetophenone, chalcone was prepared by using the Claisen-Schmidt reaction. From chalcone, benzoxazine was prepared using the Mannich reaction. Derivative of Quinazoline was prepared from benzoxazine by a reaction with sodium acetate in the presence of o-phenylene diamine. These compounds were subjected to an in vitro antioxidant assay to evaluate their efficacy in scavenging reactive oxygen species and reducing oxidative damage. Results: The results revealed that compounds T3 and T5 exhibited potent antioxidant activity, with IC50 values comparable to those of the standard antioxidant, ascorbic acid. Docking studies confirmed strong binding affinities to the active site of human peroxiredoxin, supported by favorable interactions and binding energies around -9.1 to -9.4 kcal/mol. ADME profiles indicated drug-likeness for all compounds, particularly T3 and T5. Discussion: The strong antioxidant activity of T3 and T5 can be attributed to the presence of hydroxyl and electron-donating groups, which enhance radical scavenging and stabilization. Docking results supported their biological potential through stable interactions with peroxiredoxin, a key antioxidant enzyme. ADME profiles further validated their suitability as drug candidates. These findings highlight T3 and T5 as promising leads for further development, although in vivo validation is required. Conclusion: The synthesized compounds, T3 and T5, showed potent antioxidant activity comparable to that of the standard drug, ascorbic acid. The results indicated that several synthesized quinazoline derivatives exhibited significant antioxidant activity, suggesting their potential as therapeutic agents in combating oxidative stress-related diseases. This study highlights the successful development of novel quinazoline-based antioxidants and underscores the need for further research to optimize their efficacy and explore their therapeutic applications.
Gupta et al. (Wed,) studied this question.