Antidiabetic potential of isolated compounds from Cyperus sexangularis Nees: An in silico molecular docking and dynamic-based approach

Context: Diabetes is a metabolic and chronic inflammatory disease that affects over 537 million people worldwide, with a projected rise to 783 million cases by 2045 if not put in check. Plant-derived compounds have continued to show strong anti-hyperglycemic activities with minimal adverse effects, with many more to be explored. Aims: To estimate the potential therapeutic tendencies of the phytochemicals isolated from the leaf extracts of Cyperus sexangularis against α-amylase and α-glucosidase proteins implicated in hyperglycemia. Methods: In silico molecular docking, drug-likeness profiling, and molecular dynamics (MD) studies. Results: The isolated compounds were characterized by spectroscopic means to be dodecanoic acid, ethyl nonadecanoate, ethyl stearate, β-sitosterol, and stigmasterol. The interaction of stigmasterol with the α-amylase and α-glucosidase protein displayed the binding energy score of -10.0 kcal/mol and -7.6 kcal/mol, respectively. However, the standard antidiabetic drug (acarbose) exhibited a binding energy score of -8.6 and -4.6 kcal/mol. The physicochemical characteristics of the compounds by Lipinski's rule of five and Veber's rule suggested stigmasterol and β-sitosterol as promising compounds that can further be explored against diabetes. Furthermore, at 120 ns MD simulations, the RMSD and RMSF analysis of stigmasterol-α-amylase (1), β-sitosterol-α-amylase (2), stigmasterol-α-glucosidase (3) and β-sitosterol-α-glucosidase (4) complexes showed the fewest fluctuations, indicating the conformational stability of the respective complexes. Conclusions: Identified bioactive compounds in C. sexangularis leaf extracts, notably stigmasterol and β-sitosterol, are the best-scoring lead compounds with remarkable inhibitory properties against α-amylase and α-glucosidase digestive enzymes implicated in diabetes.