Insights into the inhibitory activity and mechanism of natural compounds from Rhinacanthus nasutus on α-glucosidase through kinetic, molecular docking, and molecular dynamics studies

Rhinacathin nasutus, commonly found in the tropical regions of Africa and Asia, has demonstrated a range of pharmacological effects, including anticancer, antifungal, anti-inflammatory, anti-Alzheimer, anti-tumor, anti-Parkinson, and hypolipidemic activities. However, reports on how its secondary metabolites inhibit α-glucosidase are scarce. The phytochemical investigation on the stems of Rhinacathin nasuthus resulted in the isolation and identification of a new compound (1) together with nine known metabolites (2–10). Their structures were elucidated by spectroscopic techniques, mass spectrometry and literature values. The absolute configuration of 1 was determined through NOESY data analysis and electronic circular dichroism (ECD) spectroscopy. All isolated compounds were tested for their yeast α-glucosidase inhibitory activity, exhibiting moderate to good activity. Notably, compounds (3), (4), and betulin (8) showed potent activity toward α-glucosidase with IC50 values of 10.8, 18.6, and 6.5 µM, respectively (the positive control, acarbose, IC50 93.6 μM). This study marks the first investigation of α-glucosidase activity for compounds 3 and 4. Therefore, these compounds were chosen for kinetic studies, molecular docking, and molecular dynamics to understand their mechanism. The results from both in vitro and in silico studies suggest that compounds 3 and 4 could be promising candidates for further research in the development of new α-glucosidase inhibitors. © 2024 Elsevier B.V.