Exploring the therapeutic potential of some alkaloidal phytoconstituents for diabetes management: a thorough in-silico approachment

Abstract Background The efficacy of synthetic drugs in the treatment of diabetes mellitus often falls short, limiting their use to symptom management. Consequently, there has been an increasing fascination with alternative medicine, specifically herbal remedies. The presence of alkaloids in medicinal plants presents a promising prospect for the advancement of novel approaches to diabetes mellitus therapies. The aim of this research is to evaluate the bioactive alkaloid phytoconstituents and their interaction with the α -amylase and α -glucosidase inhibitors using in-silico approach. Results A total of 49 phytoconstituents were analyzed as potential inhibitors of these enzymes with top 15 selected based on molecular docking studies. Physicochemical properties, ADME (absorption, distribution, metabolism, and excretion) profile, and toxicity predictions were performed to predict pharmacokinetics, drug-likeness, and toxicity. Subsequently, the molecular docking study was performed using Schrodinger software (PDB ID: 3TOP). Piperumbellactam C (− 8.18 kcal/mol) and Trigonelline (− 7.99 kcal/mol). displayed the highest docking score and standard acarbose showed (− 8.97 kcal/mol). The MM-GBSA (Molecular Mechanics, General Born Surface Area) assay showed favorable binding energy. All other phytoconstituents exhibited favorable pharmacokinetic and toxicological parameters and found within acceptable ranges. Further, a 200 ns MD (Molecular Dynamic) Simulation study was carried out in order to check the stability of Piperumbellactam C-3TOP complex. Conclusions The findings of this research validate the antidiabetic properties of some active alkaloid phytoconstituents and additionally showcase the potential inhibitory activity via in-silico analysis.