Design, Synthesis, Computational Studies, and Antidiabetic Evaluation of Hydrazide Derivative: In Vitro, In Vivo and In Silico Investigation

ABSTRACT Diabetes mellitus (DM) is a group of metabolic diseases characterized by long term high blood sugar levels. This work reports the synthesis of a hydrazone Schiff base compounds based on furan‐2‐carboxylic acid by treating sulfuric acid with the starting material (furan‐2‐carboxylic acid) in ethanol solvent to get the esterified compounds. Hydrazine hydrate was then refluxed with the desired ester in ethanol solvent to get the hydrazide, which was further refluxed with 4‐fluorobenzaldehyde in ethanol containing a catalytic amount of acetic acid to get the hydrazone compound. The compound has been characterized and assessed for their in vitro α‐amylase, α‐glucosidase, antioxidant, and dipeptidyl peptidase‐IV inhibition followed by in vivo antidiabetic activity. The biological studies of the compound showed significant α‐amylase (IC 50 = 47.11) and α‐glucosidase (IC 50 = 25.91) activities superior than the standard acarbose. The compound attributed significant dipeptidyl peptidase‐IV inhibition, and also notable antioxidant potential. Furthermore, on the basis of in vitro findings this compound showed a substantial reduction of in blood glucose level in animal model and no toxicity was observed in animal model and improvement in biochemical parameters. Furthermore, the molecular docking study showed that the compound has highest binding energy with α‐amylase (−6.5) and α‐glucosidase (−6.5). Additionally, ADME analysis was performed which indicated the compound pass all rules of drug and also have high GI absorption. The synthesized compound predicted bioavailable score was high. Simulation was done for further investigation of acarbose (control) and compound 3 which result show that compound 3 is more stable as compared acarbose.