Identification of Alkaloid-Derived α-Glucosidase Inhibitors for Diabetes Management: An In Silico Approach

Abstract

Background & Objectives: Alkaloids constitute a structurally diverse class of naturally occurring compounds with a wide range of pharmacological activities. One of the principal mechanisms through which alkaloids may contribute to the management of diabetes mellitus (DM) is the inhibition of α-glucosidase. Despite their considerable therapeutic potential, the molecular interactions between alkaloids and α-glucosidase remain insufficiently characterized and warrant comprehensive investigation. Therefore, this study aimed to identify potential alkaloid-derived α-glucosidase inhibitors using an in silico approach for the management of DM.

Materials & Methods: An initial computational screening of 15 alkaloid ligands excluded cepharanthine because of predicted mutagenicity and immunotoxicity, whereas tetrandrine and fangchinoline were excluded because they failed to satisfy drug-likeness criteria. The remaining 12 compounds were subsequently subjected to molecular docking against α-glucosidase.

Results: Scopolamine exhibited the most favorable docking score (-6.91 kcal/mol), outperforming acarbose, the reference inhibitor (-6.87 kcal/mol). In the α-glucosidase and scopolamine complex, Arg699 and Glu301 participated in hydrogen bond and Pi anion interactions, respectively. Secondary structure analysis further revealed scopolamine induced conformational alterations in α-glucosidase, characterized by an increase in α-helix content and a reduction in β-sheet content, changes that were consistent with its predicted inhibitory activity.

Conclusion: These findings suggest that scopolamine is a promising candidate α-glucosidase inhibitor. Nevertheless, further in vitro and in vivo studies are required to validate its antidiabetic potential and determine its therapeutic value for controlling postprandial hyperglycemia in DM