Multitarget Action of Xanthones from <i>Garcinia mangostana</i> against α-Amylase, α-Glucosidase and Pancreatic Lipase
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...
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MDPI AG
2022-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/10/3283 |
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| author | Juan Cardozo-Muñoz Luis E. Cuca-Suárez Juliet A. Prieto-Rodríguez Fabian Lopez-Vallejo Oscar J. Patiño-Ladino |
| author_facet | Juan Cardozo-Muñoz Luis E. Cuca-Suárez Juliet A. Prieto-Rodríguez Fabian Lopez-Vallejo Oscar J. Patiño-Ladino |
| author_sort | Juan Cardozo-Muñoz |
| collection | DOAJ |
| description | 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 IC<sub>50</sub> 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. |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T03:19:30Z |
| publishDate | 2022-05-01 |
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| series | Molecules |
| spelling | doaj.art-b2dbe663f33944bf87befde87f45c2fa2023-11-23T12:24:00ZengMDPI AGMolecules1420-30492022-05-012710328310.3390/molecules27103283Multitarget Action of Xanthones from <i>Garcinia mangostana</i> against α-Amylase, α-Glucosidase and Pancreatic LipaseJuan Cardozo-Muñoz0Luis E. Cuca-Suárez1Juliet A. Prieto-Rodríguez2Fabian Lopez-Vallejo3Oscar J. Patiño-Ladino4Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Sede Bogotá, Bogotá 111321, ColombiaDepartamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Sede Bogotá, Bogotá 111321, ColombiaDepartamento de Química, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá 110231, ColombiaDepartamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Sede Bogotá, Bogotá 111321, ColombiaDepartamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Sede Bogotá, Bogotá 111321, ColombiaDigestive 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 IC<sub>50</sub> 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.https://www.mdpi.com/1420-3049/27/10/3283<i>Garcinia mangostana</i>α-amylaseα-glucosidasepancreatic lipasedigestive enzymesxanthones |
| spellingShingle | Juan Cardozo-Muñoz Luis E. Cuca-Suárez Juliet A. Prieto-Rodríguez Fabian Lopez-Vallejo Oscar J. Patiño-Ladino Multitarget Action of Xanthones from <i>Garcinia mangostana</i> against α-Amylase, α-Glucosidase and Pancreatic Lipase Molecules <i>Garcinia mangostana</i> α-amylase α-glucosidase pancreatic lipase digestive enzymes xanthones |
| title | Multitarget Action of Xanthones from <i>Garcinia mangostana</i> against α-Amylase, α-Glucosidase and Pancreatic Lipase |
| title_full | Multitarget Action of Xanthones from <i>Garcinia mangostana</i> against α-Amylase, α-Glucosidase and Pancreatic Lipase |
| title_fullStr | Multitarget Action of Xanthones from <i>Garcinia mangostana</i> against α-Amylase, α-Glucosidase and Pancreatic Lipase |
| title_full_unstemmed | Multitarget Action of Xanthones from <i>Garcinia mangostana</i> against α-Amylase, α-Glucosidase and Pancreatic Lipase |
| title_short | Multitarget Action of Xanthones from <i>Garcinia mangostana</i> against α-Amylase, α-Glucosidase and Pancreatic Lipase |
| title_sort | multitarget action of xanthones from i garcinia mangostana i against α amylase α glucosidase and pancreatic lipase |
| topic | <i>Garcinia mangostana</i> α-amylase α-glucosidase pancreatic lipase digestive enzymes xanthones |
| url | https://www.mdpi.com/1420-3049/27/10/3283 |
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