Bio-Guided Isolation of Acetogenins from <i>Annona cherimola</i> Deciduous Leaves: Production of Nanocarriers to Boost the Bioavailability Properties
Annonaceous acetogenins (ACGs) are lipophilic polyketides isolated exclusively from Annonaceae. They are considered to be amongst the most potent antitumor compounds. Nevertheless, their applications are limited by their poor solubility. The isolation of ACGs from <i>Annona cherimola</i>...
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MDPI AG
2020-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/20/4861 |
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| author | Maria Teresa Gutiérrez Alexandra G. Durán Francisco J. R. Mejías José M. G. Molinillo Diego Megias Manuel M. Valdivia Francisco A. Macías |
| author_facet | Maria Teresa Gutiérrez Alexandra G. Durán Francisco J. R. Mejías José M. G. Molinillo Diego Megias Manuel M. Valdivia Francisco A. Macías |
| author_sort | Maria Teresa Gutiérrez |
| collection | DOAJ |
| description | Annonaceous acetogenins (ACGs) are lipophilic polyketides isolated exclusively from Annonaceae. They are considered to be amongst the most potent antitumor compounds. Nevertheless, their applications are limited by their poor solubility. The isolation of ACGs from <i>Annona cherimola</i> leaves, an agricultural waste, has not been reported to date. Molvizarin (<b>1</b>) cherimolin-1 (<b>2</b>), motrilin (<b>3</b>), annonacin (<b>4</b>) and annonisin (<b>5</b>) are isolated for the first time from <i>A. cherimola</i> deciduous leaves. Annonacin was found to be four- and two-times more potent in tumoral cells (HeLa, 23.6% live cells; IGROV-1, 40.8% live cells for 24 h) than in HEK-293 at 50 µM (24 h, 87.2% live cells). Supramolecular polymer micelles (SMPMs) were synthesized to encapsulate the major ACG isolated, annonacin, in order to improve its solubility in aqueous media. The bioavailability of this compound was increased by a factor of 13 in a simulated human digestive system when compared with free annonacin and an encapsulation efficiency of 35% was achieved. In addition, the cytotoxic activity of SMPMs that hosted annonacin (100 µM, 24 h, 5.8% live cells) was increased compared with free annonacin in water (100 µM, 24 h, 92% live cells). These results highlight the use of by-products of <i>A. cherimola</i>, and their pure compounds, as a promising source of anticancer agents. The use of SMPMs as nanocarriers of ACGs could be an alternative for their application in food field as nutraceutical to enhance the administration and efficacy. |
| first_indexed | 2024-03-10T15:26:15Z |
| format | Article |
| id | doaj.art-0d5eb1c57ef5436a93e48c18f7c12c1a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T15:26:15Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-0d5eb1c57ef5436a93e48c18f7c12c1a2023-11-20T17:59:00ZengMDPI AGMolecules1420-30492020-10-012520486110.3390/molecules25204861Bio-Guided Isolation of Acetogenins from <i>Annona cherimola</i> Deciduous Leaves: Production of Nanocarriers to Boost the Bioavailability PropertiesMaria Teresa Gutiérrez0Alexandra G. Durán1Francisco J. R. Mejías2José M. G. Molinillo3Diego Megias4Manuel M. Valdivia5Francisco A. Macías6Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus de Excelencia Internacional (ceiA3), School of Science, University of Cadiz, 11510 Puerto Real, SpainAllelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus de Excelencia Internacional (ceiA3), School of Science, University of Cadiz, 11510 Puerto Real, SpainAllelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus de Excelencia Internacional (ceiA3), School of Science, University of Cadiz, 11510 Puerto Real, SpainAllelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus de Excelencia Internacional (ceiA3), School of Science, University of Cadiz, 11510 Puerto Real, SpainConfocal Microscopy Unit, Spanish National Cancer Research Center (CNIO), E-28029 Madrid, SpainDepartment of Biomedicine, Biotechnology and Public Health, School of Science, Institute of Biomolecules (INBIO), University of Cadiz, 11510 Puerto Real, SpainAllelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus de Excelencia Internacional (ceiA3), School of Science, University of Cadiz, 11510 Puerto Real, SpainAnnonaceous acetogenins (ACGs) are lipophilic polyketides isolated exclusively from Annonaceae. They are considered to be amongst the most potent antitumor compounds. Nevertheless, their applications are limited by their poor solubility. The isolation of ACGs from <i>Annona cherimola</i> leaves, an agricultural waste, has not been reported to date. Molvizarin (<b>1</b>) cherimolin-1 (<b>2</b>), motrilin (<b>3</b>), annonacin (<b>4</b>) and annonisin (<b>5</b>) are isolated for the first time from <i>A. cherimola</i> deciduous leaves. Annonacin was found to be four- and two-times more potent in tumoral cells (HeLa, 23.6% live cells; IGROV-1, 40.8% live cells for 24 h) than in HEK-293 at 50 µM (24 h, 87.2% live cells). Supramolecular polymer micelles (SMPMs) were synthesized to encapsulate the major ACG isolated, annonacin, in order to improve its solubility in aqueous media. The bioavailability of this compound was increased by a factor of 13 in a simulated human digestive system when compared with free annonacin and an encapsulation efficiency of 35% was achieved. In addition, the cytotoxic activity of SMPMs that hosted annonacin (100 µM, 24 h, 5.8% live cells) was increased compared with free annonacin in water (100 µM, 24 h, 92% live cells). These results highlight the use of by-products of <i>A. cherimola</i>, and their pure compounds, as a promising source of anticancer agents. The use of SMPMs as nanocarriers of ACGs could be an alternative for their application in food field as nutraceutical to enhance the administration and efficacy.https://www.mdpi.com/1420-3049/25/20/4861<i>Annona cherimola</i>acetogeninsby-productsencapsulationcytotoxic activitynutraceutical |
| spellingShingle | Maria Teresa Gutiérrez Alexandra G. Durán Francisco J. R. Mejías José M. G. Molinillo Diego Megias Manuel M. Valdivia Francisco A. Macías Bio-Guided Isolation of Acetogenins from <i>Annona cherimola</i> Deciduous Leaves: Production of Nanocarriers to Boost the Bioavailability Properties Molecules <i>Annona cherimola</i> acetogenins by-products encapsulation cytotoxic activity nutraceutical |
| title | Bio-Guided Isolation of Acetogenins from <i>Annona cherimola</i> Deciduous Leaves: Production of Nanocarriers to Boost the Bioavailability Properties |
| title_full | Bio-Guided Isolation of Acetogenins from <i>Annona cherimola</i> Deciduous Leaves: Production of Nanocarriers to Boost the Bioavailability Properties |
| title_fullStr | Bio-Guided Isolation of Acetogenins from <i>Annona cherimola</i> Deciduous Leaves: Production of Nanocarriers to Boost the Bioavailability Properties |
| title_full_unstemmed | Bio-Guided Isolation of Acetogenins from <i>Annona cherimola</i> Deciduous Leaves: Production of Nanocarriers to Boost the Bioavailability Properties |
| title_short | Bio-Guided Isolation of Acetogenins from <i>Annona cherimola</i> Deciduous Leaves: Production of Nanocarriers to Boost the Bioavailability Properties |
| title_sort | bio guided isolation of acetogenins from i annona cherimola i deciduous leaves production of nanocarriers to boost the bioavailability properties |
| topic | <i>Annona cherimola</i> acetogenins by-products encapsulation cytotoxic activity nutraceutical |
| url | https://www.mdpi.com/1420-3049/25/20/4861 |
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