Biochemical and Computational Insights into the Therapeutic Potencies of Quinoline Appended Imidazole Compounds

Abstract Diabetes is a complex metabolic disorder characterized by oxidative stress and chronic inflammation, necessitating the development of multifunctional therapeutic agents. This study evaluates the in vitro and in silico antihyperglycemic, antioxidant, and anti‐inflammatory activities of four 3‐(4,5‐diaryl‐1 H ‐imidazol‐2‐yl)quinoline‐2‐amine derivatives (a–d) . Among them, compound (a) exhibited strong antihyperglycemic activity, with significant α‐amylase inhibition (IC 50 = 132.55 ± 4.12 µg/mL) and enhanced glucose uptake in yeast cells (IC 50 = 126.32 ± 3.48 µg/mL). Compound (d) showed superior antioxidant (IC 50 = 42–44 µg/mL) and anti‐inflammatory (IC 50 = 132.55 ± 4.12 µg/mL) properties. Molecular docking against α‐amylase and PPAR‐γ confirmed strong binding interactions for all compounds, with compound (a) showing the collectively better affinity (−10 kcal/mol and −11.1 kcal/mol). Further, molecular dynamics in normal mode analysis validated its stability and functional potential. The ADMET predictions suggested favorable pharmacokinetics, especially for compounds (a) and (b) . The findings suggest that compound (a) has significant potential as a lead molecule for antihyperglycemic treatment with moderate antioxidant and anti‐inflammatory properties. Compound (b) also shows promise, albeit with slightly lower bioactivity. Despite these promising findings, none of the tested compounds outperformed the efficacy of standard drugs in any of the in vitro assays, indicating the need for further structural optimization to enhance their therapeutic potential.