Spatial and Energetic Stability Assessment of the Adducts of Phytocompounds of Piper longum L. with α-amylase by Computational Approach

Medicinal plants have been a rich source of bioactive compounds used in treating various diseases since ancient times. Diabetes, a long-term metabolic condition, is affecting a large portion of the global population. Hyperglycemia, which leads to diabetes mellitus, can be managed by inhibiting the human pancreatic α-amylase enzyme. This study aims to identify potential α-amylase inhibitors from Piper longum L. using different computational methods. From the molecular docking calculations, piperadione, coumaperine, and cepharanone B exhibited good binding affinities of -8.8 kcal/mol, -8.6 kcal/mol, and -8.3 kcal/mol, respectively, better than that of the reference drugs. All the adducts showed significant geometrical stability with smooth RMSD curves from 150 ns molecular dynamics simulations. The thermodynamic stability evaluated through the MMPBSA method in terms of binding free energy changes demonstrated consistent feasibility and spontaneity of the reactions. The hit candidates could be proposed for diabetes management after verification through in vitro and in vivo experiments.