Discovery of Pyrazolo[5,1-b]quinazoline Tethered 1,2,3-Triazole Analogs as Potential Antioxidant Agents: Design, Synthesis, Biological Evaluation, and In Silico Insights

Abstract

This article seeks to develop new antioxidant agents to address the rising prevalence of oxidative stress-associated disorders. This research outlines a high-yielding synthetic approach to functionalized pyrazolo[5,1-b]quinazoline tethered 1,2,3-triazole derivatives 7(a-x) using L-proline as a catalyst under microwave irradiation. The synthesized compounds were evaluated for their in vitro antioxidant activity using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical as well as hydrogen peroxide (H₂O₂) scavenging assays. In all assays, compounds 7a, 7b, 7c, 7d, 7m, 7n, 7o, and 7p exhibited significantly greater antioxidant activity compared to the reference standard, ascorbic acid. Molecular docking study reinforced the experimental findings, showing that the compounds engage in multiple binding interactions within the active sites of both enzymes. Additionally, density functional theory (DFT) analysis was also performed to examine the electronic and molecular properties of the compounds, revealing strong agreement between theoretical predictions and experimental results. Overall, the results highlight these derivatives as promising lead candidates for antioxidant drug development, supported by robust evidence from molecular docking and DFT analyses.