Synthesis and Computational Evaluation of Isoxazole-Benzimidazole Hybrids as a New Class of Antioxidants: Molecular Docking, ADMET Screening, and DFT Analysis

A series of isoxazole-benzimidazole hybrids were synthesized via click chemistry, employing the reaction of terminal alkynes with substituted aldoximes. The catalyst DBU was utilized due to its accessibility and cost-effectiveness. The newly synthesized analogues were characterized using mass spectrometry, 1H NMR, and IR spectroscopy techniques. Their antioxidant activities were evaluated through DPPH and nitric oxide scavenging assays, demonstrating significant efficacy against the tested organisms. To further support the potent antioxidant properties of compounds in silico molecular docking studies were conducted using ascorbic acid as a reference ligand extracted from the cytochrome c peroxidase enzyme (PDB code: 2X08). Additionally, in silico ADMET studies revealed that compounds exhibited no toxicity or carcinogenicity. Characterization of molecule was achieved using density functional theory (DFT) with the B3LYP/6-311++G(d, p) basis set, providing structural parameters through geometry optimization. Molecular electrostatic potential (MEP) and HOMO–LUMO energy gaps were also calculated. Thus, this approach successfully combined the bi-heterocyclic structures of isoxazole and benzimidazole using innovative copper-free, oxime-based click chemistry techniques.