DESIGN AND IN SILICO EVALUATION OF PHENOXY ACETAMIDE DERIVATIVES AS POTENTIAL ANTIDIABETIC AGENTS
DOI:
https://doi.org/10.22159/ijap.2025v17i5.54892Keywords:
Molecular docking, MM-GBSA, Phenoxy-acetamide, AMPK, ADME, Type II diabetesAbstract
Objective: This study explores the interactions of phenoxy acetamide derivatives with AMP-activated protein kinase (AMPK), a key enzyme in metabolic regulation. The goal is to evaluate the AMPK activation potential of these compounds using in silico approaches.
Methods: Molecular docking was performed using the Glide module to assess binding affinity. Binding free energy (ΔG_bind) was calculated using the MM-GBSA method, and pharmacokinetic profiles were evaluated via ADME predictions using QikProp.
Results: Among the tested compounds, 3-chlorophenyl phenoxy acetamide (compound 5) exhibited the highest XP-docking score of –5.22 kcal/mol and a ΔG_bind of –97.78 kcal/mol, indicating strong binding with the AMPK active site. Key interactions included hydrogen bonding with residues PRO127, MET84, ARG117, and TYR120. ADME analysis revealed that all compounds showed low CNS penetration (QPlog BB<–1) and acceptable intestinal absorption (Caco-2>300 nm/s).
Conclusion: Compound 5 demonstrates significant AMPK activation potential and favorable ADME properties, suggesting its promise as a lead compound for type II diabetes therapy.
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Copyright (c) 2025 INDHUMATHI S., S. SREE NITHI, GOBIANANTH, MOHD ABDUL BAQI, N. VENKATHESHAN, GANESH MEENA, KOPPULA JAYANTHI
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