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Xylitol as a Hydrophilization Moiety for a Biocatalytically Synthesized Ibuprofen Prodrug
Biocatalyzed synthesis can be exploited to produce high-value products, such as prodrugs. The replacement of chemical approaches with biocatalytic processes is advantageous in terms of environmental prevention, embracing the principles of green chemistry. In this work, we propose the covalent attach...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880498/ https://www.ncbi.nlm.nih.gov/pubmed/35216142 http://dx.doi.org/10.3390/ijms23042026 |
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author | Zappaterra, Federico Tupini, Chiara Summa, Daniela Cristofori, Virginia Costa, Stefania Trapella, Claudio Lampronti, Ilaria Tamburini, Elena |
author_facet | Zappaterra, Federico Tupini, Chiara Summa, Daniela Cristofori, Virginia Costa, Stefania Trapella, Claudio Lampronti, Ilaria Tamburini, Elena |
author_sort | Zappaterra, Federico |
collection | PubMed |
description | Biocatalyzed synthesis can be exploited to produce high-value products, such as prodrugs. The replacement of chemical approaches with biocatalytic processes is advantageous in terms of environmental prevention, embracing the principles of green chemistry. In this work, we propose the covalent attachment of xylitol to ibuprofen to produce an IBU-xylitol ester prodrug. Xylitol was chosen as a hydrophilizer for the final prodrug, enhancing the water solubility of ibuprofen. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) extensively used as an analgesic, anti-inflammatory, and antipyretic. Despite being the third-most-prescribed medicine in the world, the aqueous solubility of ibuprofen is just 21 mg/L. This poor water solubility greatly limits the bioavailability of ibuprofen. We aimed to functionalize ibuprofen with xylitol using the reusable immobilized N435 biocatalyst. Instead of a biphasic media, we proposed a monophasic reaction environment. The characterization of the IBU-xylitol ester was performed by (1)H, (13)C-NMR, DEPT, COSY, HMQC, HMBC, FTIR, and MS spectroscopy. Preliminary in vitro tests showed that this enzymatically synthesized prodrug of ibuprofen reduced the expression of the interleukin 8 genes in human bronchial epithelial cells (IB3-1) from cystic fibrosis (CF) patients. |
format | Online Article Text |
id | pubmed-8880498 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88804982022-02-26 Xylitol as a Hydrophilization Moiety for a Biocatalytically Synthesized Ibuprofen Prodrug Zappaterra, Federico Tupini, Chiara Summa, Daniela Cristofori, Virginia Costa, Stefania Trapella, Claudio Lampronti, Ilaria Tamburini, Elena Int J Mol Sci Article Biocatalyzed synthesis can be exploited to produce high-value products, such as prodrugs. The replacement of chemical approaches with biocatalytic processes is advantageous in terms of environmental prevention, embracing the principles of green chemistry. In this work, we propose the covalent attachment of xylitol to ibuprofen to produce an IBU-xylitol ester prodrug. Xylitol was chosen as a hydrophilizer for the final prodrug, enhancing the water solubility of ibuprofen. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) extensively used as an analgesic, anti-inflammatory, and antipyretic. Despite being the third-most-prescribed medicine in the world, the aqueous solubility of ibuprofen is just 21 mg/L. This poor water solubility greatly limits the bioavailability of ibuprofen. We aimed to functionalize ibuprofen with xylitol using the reusable immobilized N435 biocatalyst. Instead of a biphasic media, we proposed a monophasic reaction environment. The characterization of the IBU-xylitol ester was performed by (1)H, (13)C-NMR, DEPT, COSY, HMQC, HMBC, FTIR, and MS spectroscopy. Preliminary in vitro tests showed that this enzymatically synthesized prodrug of ibuprofen reduced the expression of the interleukin 8 genes in human bronchial epithelial cells (IB3-1) from cystic fibrosis (CF) patients. MDPI 2022-02-11 /pmc/articles/PMC8880498/ /pubmed/35216142 http://dx.doi.org/10.3390/ijms23042026 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zappaterra, Federico Tupini, Chiara Summa, Daniela Cristofori, Virginia Costa, Stefania Trapella, Claudio Lampronti, Ilaria Tamburini, Elena Xylitol as a Hydrophilization Moiety for a Biocatalytically Synthesized Ibuprofen Prodrug |
title | Xylitol as a Hydrophilization Moiety for a Biocatalytically Synthesized Ibuprofen Prodrug |
title_full | Xylitol as a Hydrophilization Moiety for a Biocatalytically Synthesized Ibuprofen Prodrug |
title_fullStr | Xylitol as a Hydrophilization Moiety for a Biocatalytically Synthesized Ibuprofen Prodrug |
title_full_unstemmed | Xylitol as a Hydrophilization Moiety for a Biocatalytically Synthesized Ibuprofen Prodrug |
title_short | Xylitol as a Hydrophilization Moiety for a Biocatalytically Synthesized Ibuprofen Prodrug |
title_sort | xylitol as a hydrophilization moiety for a biocatalytically synthesized ibuprofen prodrug |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880498/ https://www.ncbi.nlm.nih.gov/pubmed/35216142 http://dx.doi.org/10.3390/ijms23042026 |
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