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

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Organic Synthesis

Background:

• Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia.
• Developing novel therapeutic agents with improved efficacy and safety profiles is crucial for diabetes management.
• Schiff bases and hydrazone derivatives have shown promise as antidiabetic agents.

Purpose of the Study:

• To synthesize and characterize a novel hydrazone Schiff base compound derived from furan-2-carboxylic acid.
• To evaluate the in vitro antidiabetic potential, including enzyme inhibition and antioxidant activity.
• To assess the in vivo antidiabetic efficacy and safety profile of the synthesized compound.

Main Methods:

• Synthesis of the hydrazone Schiff base compound via esterification, hydrazide formation, and condensation reactions.
• In vitro assays for α-amylase, α-glucosidase, antioxidant, and dipeptidyl peptidase-IV inhibition.
• In vivo antidiabetic study in an animal model, including toxicity and biochemical parameter assessment.
• Molecular docking and ADME/simulation studies to predict binding interactions and pharmacokinetic properties.

Main Results:

• The synthesized compound demonstrated significant in vitro inhibition of α-amylase (IC50 = 47.11) and α-glucosidase (IC50 = 25.91), outperforming the standard drug acarbose.
• The compound exhibited notable dipeptidyl peptidase-IV inhibition and antioxidant potential.
• In vivo studies revealed substantial reduction in blood glucose levels with no observed toxicity in the animal model, alongside improved biochemical parameters.
• Molecular docking indicated strong binding affinity with α-amylase and α-glucosidase (-6.5 kcal/mol).
• ADME analysis suggested favorable drug-likeness, high gastrointestinal absorption, and bioavailability.
• Simulation studies indicated greater stability for the synthesized compound compared to acarbose.

Conclusions:

• The novel hydrazone Schiff base compound possesses significant in vitro and in vivo antidiabetic activities.
• The compound's mechanism of action involves inhibition of key carbohydrate-metabolizing enzymes and antioxidant effects.
• Its favorable pharmacokinetic profile and stability suggest potential as a therapeutic agent for diabetes mellitus.