Multitarget Action of Xanthones from <i>Garcinia mangostana</i> against α-Amylase, α-Glucosidase and Pancreatic Lipase

• 出版年: Molecules
• 主要な著者: Juan Cardozo-Muñoz, Luis E. Cuca-Suárez, Juliet A. Prieto-Rodríguez, Fabian Lopez-Vallejo, Oscar J. Patiño-Ladino
• フォーマット: 論文
• 言語: 英語
• 出版事項: MDPI AG 2022-05-01
• 主題: <i>Garcinia mangostana</i>; α-amylase; α-glucosidase; pancreatic lipase; digestive enzymes; xanthones
• オンライン･アクセス: https://www.mdpi.com/1420-3049/27/10/3283

Digestive enzymes such α-amylase (AA), α-glucosidase (AG) and pancreatic lipase (PL), play an important role in the metabolism of carbohydrates and lipids, being attractive therapeutic targets for the treatment of type 2 diabetes and obesity. <i>Garcinia mangostana</i> is an interesting species because there have been identified xanthones with the potential to inhibit these enzymes. In this study, the multitarget inhibitory potential of xanthones from <i>G. mangostana</i> against AA, AG and PL was assessed. The methodology included the isolation and identification of bioactive xanthones, the synthesis of some derivatives and a molecular docking study. The chemical study allowed the isolation of five xanthones (<b>1</b>–<b>5</b>). Six derivatives (<b>6</b>–<b>11</b>) were synthesized from the major compound, highlighting the proposal of a new solvent-free methodology with microwave irradiation for obtaining aromatic compounds with tetrahydropyran cycle. Compounds with multitarget activity correspond to <b>2</b>, <b>4</b>, <b>5</b>, <b>6</b> and <b>9</b>, highlighting <b>6</b> with IC₅₀ values of 33.3 µM on AA, 69.2 µM on AG and 164.4 µM on PL. Enzymatic kinetics and molecular docking studies showed that the bioactive xanthones are mainly competitive inhibitors on AA, mixed inhibitors on AG and non-competitive inhibitors on PL. The molecular coupling study established that the presence of methoxy, hydroxyl and carbonyl groups are important in the activity and interaction of polyfunctional xanthones, highlighting their importance depending on the mode of inhibition.