Molecular Docking Studies on Isolated and Characterized Compounds of Marine and Plant Origin with Antidiabetic Activity

Introduction: Diabetics Mellitus is a chronic disease characterized by hyperglycemia and disturbance in protein and fat metabolism. This study was carried out to determine the binding affinity of some marine and plant-derived compounds earlier reported through molecular docking studies, and also to evaluate the physicochemical, pharmacokinetic and toxicity profiles of these compounds.

Methods: The identified compounds with antidiabetic activities from the literature were subjected to virtual screening and rigid molecular docking in order to evaluate their binding affinity with the human PPAR alpha ligand binding domain (PDB Code: 3VI8) as the target. MMFF94 force field was used for energy minimization of the ligand molecule. The prepared compounds were then subjected to interact with the receptor through molecular docking. The toxicity, pharmacokinetics and physicochemical profiles were established using online webservers Protox 11 and SwissADME.

Results: Compounds; 6, 7, 12, 32, 66, 80, 89, 121, 138 and, 139 showed greater binding affinity with PPARy target protein with free binding energy of (-6.2 to 8.1kcal/ mol) comparable to the standard drug with 5.2kcal/mol. Similarly, the selected compounds possess acceptable physicochemical and toxicity profiles with potential for good oral bioavailability.

Conclusion: Ten (10) compounds extracted from seven (7) naturally occurring (marine) species were found as potential peroxisome proliferators-activated receptor gamma (PPARγ) agonist with promising antidiabetic activity. The in-silico studies confirmed that the 10 selected compounds have strong binding interactions with the drug receptors and therefore possess anti diabetic activity.