6-O-acetyldaidzen and frangulin B from Halodule uninervis as novel α-amylase inhibitors: A molecular dynamics...

Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose levels, and it poses significant health challenges globally. An established way of managing diabetes is through the use of α-amylase inhibitors. This study aimed to identify novel α-amylase inhibitors from phytochemicals identified from Halodule uninervis rhizomes for the control of postprandial blood glucose levels in individuals with type 2 diabetes. HRLCMS- and GCMS- identified analytes were screened on the basis of their ADME properties. Further screening was carried out on the basis of site-specific molecular docking with the α-amylase target and ligand combinations. The top 5 ranked dockings of each of the targets were further subjected to molecular dynamics simulations and analysis. On the basis of screening and molecular dynamics simulations, a glycosyloxyisoflavone, 6"-O-acetyldaidizen (6OAD) and an anthraquinone, frangulin B were found to be potential inhibitors of α-amylase on the basis of their interactions with the catalytic triad: ASP-197, GLU-233 and ASP-300. They interact via stable hydrogen bonding interactions with these residues at the enzymatic cleavage site of glycosylation. These findings suggest that 6"-O-acetyldaidizen (6OAD) and frangulin B possess both structural and dynamic attributes that are favourable for their use as putative type II diabetes therapeutics, via the regulation of postprandial glucose levels.