Sustainable Synthesis and Medicinal Profiling of Azo‐Anchored Imidazo[4,5‐ b ]Indole Scaffolds: DFT Studies, Electrochemical Sensing, and Pharmacokinetic Evaluation

ABSTRACT The synthesis of azo‐anchored imidazo[4,5 ‐b ]indoles represents a promising advancement in therapeutic and sensor technologies, offering significant potential in biomedical applications. This study presents a sustainable, high‐yield approach grounded in green chemistry, employing minimal catalyst loading for ecological compatibility. The methodology involves condensing para ‐amino‐functionalized azo benzene, aryl aldehydes, indoline‐2,3‐dione, and ammonium acetate using L‐proline as a catalyst under ultrasonic irradiation at room temperature. The electrochemical characterization via . Cyclic voltammetry (CV) on a TiO 2 .SiO 2 ‐HMS/GCE electrode revealed enhanced electrocatalytic performance, with the effective surface area increasing from 0.031 cm 2 to 0.087 cm 2 . Optimal activity was achieved at pH 6.54 with CTAB, providing a detection range of 1.0 × 10 –6 M to 5.0 × 10 –6 M, a detection limit of 1.50 × 10 –7 M, and a correlation coefficient of 0.992, indicative of irreversible reactions. Remarkably, DFT studies at the B3LYP/6‐311 G level provided qualitative insights into the favorable electronic properties via . HOMO–LUMO analysis. Molecular docking predicted that compound 5(f) may interact favorably with the SARS‐CoV‐2 spike protein, showing better docking scores than Chloroquine and Hydroxychloroquine. Molecular dynamics (MD) simulations further confirmed the stability and persistence of these protein–ligand interactions over time. This prediction is further supported by its favorable pharmacokinetic profile and measurable in vitro cytotoxicity against HEK‐293 cells, aligning computational findings with biological activity. This study highlights the dual functionality of these derivatives in sensor and therapeutic domains, adhering to green chemistry principles.