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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...

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Autores principales: Zappaterra, Federico, Tupini, Chiara, Summa, Daniela, Cristofori, Virginia, Costa, Stefania, Trapella, Claudio, Lampronti, Ilaria, Tamburini, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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