<i>In silico</i> inhibition mechanism of <i>α</i> -amylase and <i>α</i> -glucosidase by fragransinic acid and bellericagenin B, two compounds from <i>Combretum fragrans</i> F. Hoffm (Combretaceae)

Abstract Diabetes mellitus remains a global health challenge, necessitating novel therapeutic strategies to manage postprandial hyperglycemia. Inhibition of carbohydrate-hydrolyzing enzymes represents a key approach. This study investigates the inhibitory potential of phytochemicals from Combretum fragrans , a Cameroonian medicinal plant traditionally used for diabetes, against these enzymes. Five triterpenoids fragransinic acid ( 1 ), betulin ( 2 ), betulinic acid ( 3 ), bellericagenin B ( 4 ), and a mixture of β -sitosterol ( 5 ) and stigmasterol ( 6 ) were evaluated via molecular docking using HYBRID and FRED protocols. The crystal structures of α -amylase (PDB ID: 1B2Y) and α -glucosidase (PDB ID: 2QMJ) were prepared, and acarbose served as a reference inhibitor. Docking validation confirmed the reliability of the protocols (RMSD &lt; 2 Å). Compounds 1 and 4 exhibited notable binding affinities, with HYBRID scores of −5.6 and −3.7 kcal/mol for α -glucosidase, and −8.1 and −7.3 kcal/mol for α -amylase, respectively. Key interactions included hydrogen bonds with catalytic residues (ASP443, THR205) and extensive Pi–alkyl interactions with aromatic residues (TYR299, TRP539, PHE575). All the compounds demonstrated selective binding modes, suggesting competitive inhibition. This study highlights the potential of C. fragrans triterpenoids as α -amylase and α -glucosidase inhibitors, providing a structural basis for further phytochemical optimization in antidiabetic drug discovery.