Molecular Interactions and Pharmacological Evaluation of Quinoline-Imidazole Derivatives: an In Vitro and In Silico Approach

Objective: This study aimed to evaluate four 3-(4,5-diaryl-1H-imidazol-2-yl)quinoline-2-amine derivatives (Ia–Id) for their potential in diabetes management using in vitro and in silico analyses. Methods: The antihyperglycemic activity of the derivatives was assessed through glucose uptake and α-amylase inhibition assays. Antioxidant properties were evaluated using DPPH, ABTS, and phosphomolybdenum assays, while anti-inflammatory activity was determined via albumin denaturation inhibition. In silico docking studies were conducted to assess binding affinities with PPAR-γ and α-amylase. Additionally, ADMET analysis was performed to predict pharmacokinetics and toxicity profiles. Results and Discussion: Compound Ib exhibited the highest glucose uptake (58.01% at 160 µg/mL) and α-amylase inhibition (48.85% at 160 µg/mL), supported by strong docking affinities for PPAR-γ and α-amylase. Antioxidant assays identified compounds Ib and Ia as the most effective derivatives, with notable DPPH, ABTS, and phosphomolybdenum activity. Anti-inflammatory activity, evaluated through albumin denaturation inhibition, further supported the therapeutic potential of Ib and Ia. ADMET analysis predicted favorable pharmacokinetics and low toxicity for all derivatives, with Ib and Ia demonstrating higher bioavailability. Conclusions: Compound Ib emerged as the most promising candidate for diabetes management, demonstrating strong antihyperglycemic, antioxidant, and anti-inflammatory activities, along with favorable pharmacokinetic and safety profiles. These findings highlight the therapeutic potential of these derivatives and provide a foundation for future in vivo studies and structural optimization to enhance efficacy and safety in diabetes management.