Mangosteen Metabolites as Promising Alpha-Amylase Inhibitor Candidates: In Silico and In Vitro Evaluations

Abdelsattar M Omar; Dana F AlKharboush; Khadijah A Mohammad; Gamal A Mohamed; Hossam M Abdallah; Sabrin R M Ibrahim

doi:10.3390/metabo12121229

Mangosteen Metabolites as Promising Alpha-Amylase Inhibitor Candidates: In Silico and In Vitro Evaluations

Metabolites. 2022 Dec 7;12(12):1229. doi: 10.3390/metabo12121229.

Authors

Abdelsattar M Omar^{1

2

3}, Dana F AlKharboush¹, Khadijah A Mohammad¹, Gamal A Mohamed⁴, Hossam M Abdallah^{4

5}, Sabrin R M Ibrahim^{6

7}

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
³ Center for Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁴ Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁵ Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
⁶ Department of Chemistry, Preparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia.
⁷ Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.

Abstract

Diabetes is a chronic metabolic disorder characterized by raised glucose levels in the blood, resulting in grave damage over time to various body organs, including the nerves, heart, kidneys, eyes, and blood vessels. One of its therapeutic treatment approaches involves the inhibition of enzymes accountable for carbohydrate digestion and absorption. The present work is aimed at evaluating the potential of some reported metabolites from Garcinia mangostana (mangosteen, Guttiferae) as alpha-amylase inhibitors. Forty compounds were assessed for their capacity to inhibit alpha-amylase using in silico studies as well as in vitro assays. Molecular docking was carried out to analyze their binding capacities in the 3D structure of alpha-amylase (PDB ID: 4GQR). Among the tested compounds, 6-O-β-D-glucopyranosyl-2,4,6,3',4',6'-hexahydroxybenzophenone (8), aromadendrin-8-C-glucoside (5), epicatechin (6), rhodanthenone (4), and garcixanthone D (40) had a high XP G.score and a Glide G.score of -12.425, -11.855, -11.135, and -11.048 Kcal/mol, respectively. Compound 8 possessed the XP and Glide docking score of -12.425 Kcal/mol compared to the reference compounds myricetin and acarbose which had an XP and Glide docking score of -12.319 and 11.201 Kcal/mol, respectively. It interacted through hydrogen bond formations between its hydroxyl groups and the residues His 101, Asp 197, Glu 233, Asp 300, and His 305, in addition to water bridges and hydrophobic interactions. Molecular mechanics-generalized born surface area (MM-GBSA) was used to calculate the binding free energy and molecular dynamic studies that indicated the stability of the alpha-amylase-compound 8 complex during the 100 ns simulation in comparison with myricetin- and acarbose-alpha-amylase complexes. Additionally, the in vitro alpha-amylase inhibition assay findings validated the in silico study's findings. This could further validate the potential of G. mangostana as a candidate for diabetes management.

Keywords: Garcinia mangostana; alpha-amylase; diabetes; industrial development; molecular docking; molecular dynamics; xanthones.

Grants and funding

RG-37-166-43/The Deanship of Scientific Research (DSR) at King Abdulaziz University (KAU), Jeddah, Saudi Arabia has funded this project, under grant no. (RG-37-166-43)