COMBINED In-silico AND In-vitro APPROACHES TO EVALUATE THE INHIBITORY THE POTENTIAL OF BIFLAVONOIDS FROM ARAUCARIA PLANTS AGAINST α-GLUCOSIDASE AS TARGET PROTEIN

Abstract

Biflavonoids are dimers of flavonoids created by a covalent connection of C-C or C-O-C between two flavonoids and have been found to have a variety of pharmacological effects, including the ability to treat diabetes mellitus (DM). In the current investigation, the inhibitory effect of biflavonoids extracted from Araucaria hunsteinii K. Schum towards the target protein α-glucosidase was assessed using a combination of in-vitro experiments and in-silico molecular docking approach. The biflavonoids' inhibition properties were contrasted with those of acarbose, a widely used pharmaceutical for treating type 2 DM. AutoDock Vina was employed to analyze the conformational sites and docking parameters, such as binding affinity and inhibition constant. In-silico studies showed that biflavonoids effectively interacted with the active site of the α-glucosidase enzyme, which is in charge of cleaving not only bonding of the α1,4 but also the α-1,6 glycosidic on the exterior of amylose or amylopectin residues to obtain simple sugars. The docking experiments revealed that biflavonoids had tighter binding forces than acarbose against α-glucosidase. The selected biflavonoids, 7-O-methylcupressuflavone; 7,7"-di-O-methylagathisflavone, 4′,4′′′-di-O-methylamentoflavone and 4''',7-di-O-methylcupresuflavone showed an IC50 of 78.32±0.52; 388.39±0.68; 389.76±1.55 and 537.98±2,35 µM, respectively. These biflavonoids had a low binding affinity and more hydrogen bond interactions with the target enzyme, which had several important amino acid residues. The effectiveness of these compounds in inhibiting the enzyme may be explained by some of their hydrophobic interactions. Therefore, the study comes to the conclusion that biflavonoids are prospective antidiabetic agents and should be taken into consideration when developing candidates for new antidiabetic medicines.