Two new benzophenones: garcimangophenones A (6) and B (7) and five formerly reported metabolites were purified from the pericarps EtOAc fraction of Garcinia mangostana ((GM) Clusiaceae). Their structures were characterized by various spectral techniques and by comparing with the literature. The α-amylase inhibitory (AAI) potential of the isolated metabolites was assessed. Compounds 7 and 6 had significant AAI activity (IC50 9.3 and 12.2 µM, respectively) compared with acarbose (IC50 6.4 µM, reference α-amylase inhibitor). On the other hand, 5 had a moderate activity. Additionally, their activity towards the α-amylase was assessed utilizing docking studies and molecular dynamics (MD) simulations. The docking and predictive binding energy estimations were accomplished using reported crystal structure of the α-amylase (PDB ID: 5TD4). Compounds 7 and 6 possessed highly negative docking scores of -11.3 and -8.2 kcal/mol, when complexed with 5TD4, respectively while acarbose had a docking score of -16.1 kcal/mol, when complexed with 5TD4. By using molecular dynamics simulations, the compounds stability in the complexes with the α-amylase was analyzed, and it was found to be stable over the course of 50 ns. The results suggested that the benzophenone derivative 7 may be potential α-amylase inhibitors. However, further investigations to support these findings are required.
Keywords: Clusiaceae; Garcinia mangostana; amylase inhibitory; benzophenones; diabetes; docking study; molecular dynamics.