Identification of Potential Anti-Diabetic Ligands from Argemone mexicana Leaf-Derived Compounds Using Molecular Docking and Pharmacophore Modelling

Argemone mexicana has been traditionally utilized as an emetic, demulcent, and laxative. This research aimed to investigate the anti-diabetic capabilities of phytochemicals isolated by examining their effects on Peroxisome Proliferator-Activated Receptors-α, Peroxisome Proliferator-Activated Receptors-γ, Peroxisome Proliferator-Activated Receptors-δ, Dipeptidyl Peptidase-4, α-glucosidase, and α-amylase using in-silico methods. Molecular docking was performed using Autodock Vina to assess binding affinities and identify the most potent ligand. The nine ligands were 1-Pentofuranosyl-1H-1,2,4-triazole [1], (Z)-4-(2,4-Dihydroxy-2,6,6-trimethylcyclohex-1-en-1-yl) but-2-enoic acid [2a], 3-(2,3-Dihydroxy-3,5,5-trimethylcyclohex-2-en-1-yl) prop-2-enal, [2b], (3S,5R,6R,7E)-3,5,6-Trihydroxy-7-megastigmen-9-one [3], Rhein [4], Tamarixetin 3-O-β-D-glucoside [5], 2-(3-Hydroxy-4-methoxyphenyl)-3-(β-D-glucopyranosyloxy)-5,7-dihydroxy-4H-1-benzopyran-4-one [6], 2-(3,4-Dihydroxy-5-methoxyphenyl)-5,7-dihydroxy-3-(3,4,5-trihydroxy-6-methyloxan-2-yl) oxychromen-4-one [7], Palmitic acid [8]. The ligand-receptor interactions were visualized using Discovery Studios 2024, and their Pharmacokinetic properties, Water Solubility, Drug likeness, etc., were investigated using SWISSADME. Docking scores revealed that Rhein, in both targeted and blind docking, had the highest binding affinities for all six receptors (-8.1 to -9.1 kcal/mol) while palmitic acid had the lowest (-2.7 to -6.5 kcal/mol). Physicochemical property analysis indicated that most compounds had acceptable profiles, but only Rhein satisfied the key drug-likeness rules (Lipinski, Veber, Egan, and lead-likeness). Docking findings indicated that the bioactive compounds demonstrate considerable binding affinity, suggesting potential anti-diabetic properties. The findings suggest that Argemone mexicana could serve as a natural source of bioactive compounds with anti-diabetic potential. Its ability to act on multiple biological targets highlights its relevance not only in blood sugar control but also in addressing the complications associated with diabetes. These results provide a strong basis for further research to validate its effectiveness, safety, and explore its development into plant-based therapeutic options.