In-vitro and in-silico evaluation of antihyperglycemic, antioxidant, anti-inflammatory activities of selected (2Z)-2-((E)(2′hydroxy)-4 (benzylideneamino)phenyl)-3-(1-methyl-1H-imidazole-2-yl) acrylonitrile derivatives

Diabetes mellitus, characterized by impaired glucose metabolism, is a global health issue that necessitates the development of effective treatments. Acrylonitrile derivatives have emerged as promising candidates due to their diverse biological activities. This study investigates for the anti-hyperglycemic, antioxidant, and antiinflammatory properties of five acrylonitrile derivatives (a-e) and evaluates their pharmacokinetic profiles. The anti-hyperglycemic activity was evaluated by alpha-amylase inhibition and measuring glucose uptake in yeast cells. The antioxidant potential was determined using DPPH, ABTS, and phosphomolybdenum assays, and the anti-inflammatory activity was assessed using the albumin denaturation inhibition assay. Molecular docking studies were conducted to analyze binding affinities to alpha-amylase and PPAR-gamma, and ligand efficiency calculations were used to evaluate binding efficacy. Furthermore, in-silico ADMET predictions were used to assess pharmacokinetics and safety. Compound (e) (naphthalen-1-yl methyleneamino substitution) was the most effective in increasing glucose uptake (IC50 117.25 +/- 3.97 mu g/mL), inhibiting alpha-amylase (IC50 144.70 +/- 3.82 mu g/mL), and providing good antioxidant and anti-inflammatory properties. The compound demonstrated high binding affinity to PPAR-gamma and favorable pharmacokinetic properties, including high gastrointestinal absorption and no predicted toxicity. These findings suggest that compound (e) with further structural optimization would be a promising candidate for future development in the treatment of diabetes and related metabolic disorders.