Mechanistic study of α-mangostin derivatives as potent α-glucosidase inhibitors
Issued Date
2025-01-01
Resource Type
ISSN
13811991
eISSN
1573501X
Scopus ID
2-s2.0-85218689998
Journal Title
Molecular Diversity
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular Diversity (2025)
Suggested Citation
Sanachai K., Chamni S., Nutho B., Khammuang S., Ratha J., Choowongkomon K., Puthongking P. Mechanistic study of α-mangostin derivatives as potent α-glucosidase inhibitors. Molecular Diversity (2025). doi:10.1007/s11030-025-11141-6 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/105522
Title
Mechanistic study of α-mangostin derivatives as potent α-glucosidase inhibitors
Corresponding Author(s)
Other Contributor(s)
Abstract
α-Glucosidase inhibitors (AGIs) are pharmacological agents commonly used to manage postprandial hyperglycemia associated with type 2 diabetes mellitus (T2DM). Developing novel, potent AGIs remains a significant area of research. In this study, we investigated a series of derivatives of the natural product from α-mangostin as potential AGIs. A combined experimental and computational approach was employed to characterize promising compounds with potent α-glucosidase inhibitory activity. We found that α-mangostin (AM) and its derivatives (AM1 − 3) exhibited micromolar range α-glucosidase inhibition (IC50 ranging from 15.14 to 67.81 µM), surpassing the known drug acarbose (IC50 of 197.09 µM). Among the derivatives, AM1 exhibited the most promising α-glucosidase inhibition, displaying competitive inhibition kinetics with a Ki value of 47.04 µM. Molecular docking and molecular dynamics (MD) simulations provided mechanistic insights into the binding interactions between AM1 and the α-glucosidase active site. AM1 was observed to form hydrogen bonds and hydrophobic interactions with key amino acid residues within the enzyme’s active site. The introduction of amine groups in compound AM1 enhanced activity compared to AM, the parent compound. This study highlights the potential of α-mangostin derivatives as potent AGIs. The identified lead compound, AM1, warrants further investigation to assess its efficacy and safety in managing T2DM.