IN SILICO AND IN VITRO OF BIFLAVONOID FROM ARAUCARIA GENUS PLANTS AGAINST \( \alpha \)-GLUCOSIDASE ENZYME AS TARGET PROTEIN
Purwantiningsih Sugita(1*), Selvia Dwi Putri Handayani(1), Dhea Demitri Agusta(1), Laksmi Ambarsari(2), Hanhan Dianhar(3), and Dyah Utami Cahyaning Rahayu(4)

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, IPB University, Bogor, Indonesia 16680
(2)Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University, Bogor, Indonesia 16680
(3)Chemistry Study Program, Faculty of Mathematics and Natural Sciences, Universitas Negeri Jakarta, Jakarta 13220, Indonesia
(4)Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Depok 16424, Indonesia

Abstract

Biflavonoids are dimers of flavonoids formed by a covalent bond (C-C or C-O-C) between two monoflavonoids. Biflavonoids are reported to exhibit many pharmacological activities, including anti-diabetic capabilities. The research aims to determine the biflavonoids inhibitory affinity potential against the \( \alpha \)-glucosidase as a target protein through in silico and in vitro experiments. The inhibitory characteristics of the compounds were compared to that of ordinary acarbose, a diabetes type 2 treatment. AutoDock Vina was employed to analyze the conformational sites and docking parameters such as binding affinity, and inhibition constant. The compounds for the in vitro inhibitory experiment used biflavonoids from isolated from Araucaria hunsteinii K. Schum result which then, compared to the in silico study. The docking experiments revealed that biflavonoids had tighter binding forces than acarbose againts \( \alpha \)-glucosidase. The chosen biflavonoids exhibited effective concentration-dependent inhibition of the \( \alpha \)-glucosidase in vitro. The 7-O-methylcupressuflavone- 7,\( 7^{\prime}\)\(^{\prime}\)\(^{\prime}\)-di-O-methylcupresuflavone- 7,\( 7^{\prime}\)\(^{\prime}\)-di-O-methylagathisflavon, and \(4^{\prime}\),\(4^{\prime}\)\(^{\prime}\)\(^{\prime}\)-di-O-methylamentoflavone with IC50 values are 78.32\( \pm \)0.52, 537.98\( \pm \)2.35, 388.39\( \pm \)0.68, and 389.76\( \pm \)1.55 \( \mu \)M, respectively, were found to be potent and selective inhibitors of the enzyme. With the target enzyme, these compounds formed many strong hydrogen bonds with multiple key amino acid residues. Some hydrophobic interactions could explain the efficacy of these compounds in blocking the enzyme. These in vitro analyses and molecular docking studies could be further developed as potent \( \alpha \)-glucosidase inhibitors for treating diabetes mellitus.

Keywords: Biflavonoids, \( \alpha \)-Glucosidase, Binding affinity, Inhibition constant, Amino acid residues

Topic: Natural Products and Biological Chemistry