Evaluation of in vitro and in silico antihyperglycemic, antioxidant, anti-inflammatory potencies of selected quinoline-imidazole hybrids

Abstract

In this study, a series of previously synthesized 3-(4,5-diaryl-1H-imidazol-2-yl)quinoline-2-amine derivatives (compounds a-d) were evaluated for their antihyperglycemic, antioxidant, and anti-inflammatory activities through in vitro and in silico approaches. Compound b (with a methyl group) inhibited α-amylase (IC50 = 115.88 µg/mL), but not as strongly as the standard drug acarbose (IC50 = 91.26 µg/mL). Kinetic studies indicated that compound b follows a mixed competitive inhibition mechanism, differing from acarbose’s competitive inhibition. Normal mode analysis further confirmed the stable binding of compound b to α-amylase. Compound b improved glucose uptake (IC50 = 117.25 µg/mL), though not as effectively as the standard antidiabetic drug pioglitazone (IC50 = 97.61 µg/mL). Compound c (chloro-substituted) showed strong antioxidant activity in DPPH (IC50 = 46.16 µg/mL) and ABTS+ (IC50 = 47.57 µg/mL) assays, though less potent than ascorbic acid (IC50 ≈ 26 µg/mL). It also exhibited good anti-inflammatory activity (IC50 = 214.45 µg/mL), while diclofenac sodium showed superior inhibition (IC50 = 122.66 µg/mL). Molecular docking confirmed strong interactions with α-amylase and PPAR-γ, with compound b displaying the lowest binding energies (-10.0 and − 11.1 kcal/mol, respectively). ADMET predictions suggested that compounds a (unsubstituted) and b possess favorable pharmacokinetic properties, including high gastrointestinal absorption and compliance with Lipinski’s rule of five, while compound d (methyl and chlorine substituted) exhibited poor solubility and potential respiratory toxicity. Although the tested compounds demonstrated efficacy comparable to standard drugs, further structural modifications are necessary to optimize their potency and therapeutic performance.