Biocatalytic Insights for The Synthesis of New Potential Prodrugs: Design of two Ibuprofen Derivatives
Due to its effectiveness, ibuprofen is one of the most popular anti-inflammatory drugs worldwide. However, the poor water solubility of this active ingredient severely limits its spectrum of pharmaceutical formulations (and often results in severe adverse effects due to high administered doses). To...
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ftmdpi:oai:mdpi.com:/2076-3417/13/17/9852/ 2023-10-01T03:52:09+02:00 Biocatalytic Insights for The Synthesis of New Potential Prodrugs: Design of two Ibuprofen Derivatives Federico Zappaterra Francesco Presini Valentina Venturi Lindomar Alberto Lerin Pier Paolo Giovannini Stefania Costa agris 2023-08-31 application/pdf https://doi.org/10.3390/app13179852 eng eng Multidisciplinary Digital Publishing Institute Applied Biosciences and Bioengineering https://dx.doi.org/10.3390/app13179852 https://creativecommons.org/licenses/by/4.0/ Applied Sciences Volume 13 Issue 17 Pages: 9852 ibuprofen NSAID erythritol glycerol esterification lipase prodrug derivative Text 2023 ftmdpi https://doi.org/10.3390/app13179852 2023-09-03T23:54:32Z Due to its effectiveness, ibuprofen is one of the most popular anti-inflammatory drugs worldwide. However, the poor water solubility of this active ingredient severely limits its spectrum of pharmaceutical formulations (and often results in severe adverse effects due to high administered doses). To overcome these limitations, in this work, we enzymatically synthesized more hydrophilic derivatives of ibuprofen through its covalent attachment to two biobased polyalcohols: erythritol and glycerol. Herein, we report the optimized reaction conditions to produce an IBU–erythritol ester (82% ± 4% of conversion) by using Candida antarctica lipase B (CalB). Furthermore, we also report the enantioselective solventless esterification of (S)-ibuprofen with glycerol (83% ± 5% of conversion), exploiting immobilized Rhizomucor miehei lipase as a biocatalyst. The full NMR characterizations of the prodrug esters were performed via 1H, 13C-NMR, DEPT, COSY, HSQC, and HMBC-NMR. The approach reported in this work can be extended to a large variety of poorly water-soluble active pharmaceutical ingredients (APIs). Text Antarc* Antarctica MDPI Open Access Publishing Applied Sciences 13 17 9852 |
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MDPI Open Access Publishing |
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English |
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ibuprofen NSAID erythritol glycerol esterification lipase prodrug derivative |
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ibuprofen NSAID erythritol glycerol esterification lipase prodrug derivative Federico Zappaterra Francesco Presini Valentina Venturi Lindomar Alberto Lerin Pier Paolo Giovannini Stefania Costa Biocatalytic Insights for The Synthesis of New Potential Prodrugs: Design of two Ibuprofen Derivatives |
topic_facet |
ibuprofen NSAID erythritol glycerol esterification lipase prodrug derivative |
description |
Due to its effectiveness, ibuprofen is one of the most popular anti-inflammatory drugs worldwide. However, the poor water solubility of this active ingredient severely limits its spectrum of pharmaceutical formulations (and often results in severe adverse effects due to high administered doses). To overcome these limitations, in this work, we enzymatically synthesized more hydrophilic derivatives of ibuprofen through its covalent attachment to two biobased polyalcohols: erythritol and glycerol. Herein, we report the optimized reaction conditions to produce an IBU–erythritol ester (82% ± 4% of conversion) by using Candida antarctica lipase B (CalB). Furthermore, we also report the enantioselective solventless esterification of (S)-ibuprofen with glycerol (83% ± 5% of conversion), exploiting immobilized Rhizomucor miehei lipase as a biocatalyst. The full NMR characterizations of the prodrug esters were performed via 1H, 13C-NMR, DEPT, COSY, HSQC, and HMBC-NMR. The approach reported in this work can be extended to a large variety of poorly water-soluble active pharmaceutical ingredients (APIs). |
format |
Text |
author |
Federico Zappaterra Francesco Presini Valentina Venturi Lindomar Alberto Lerin Pier Paolo Giovannini Stefania Costa |
author_facet |
Federico Zappaterra Francesco Presini Valentina Venturi Lindomar Alberto Lerin Pier Paolo Giovannini Stefania Costa |
author_sort |
Federico Zappaterra |
title |
Biocatalytic Insights for The Synthesis of New Potential Prodrugs: Design of two Ibuprofen Derivatives |
title_short |
Biocatalytic Insights for The Synthesis of New Potential Prodrugs: Design of two Ibuprofen Derivatives |
title_full |
Biocatalytic Insights for The Synthesis of New Potential Prodrugs: Design of two Ibuprofen Derivatives |
title_fullStr |
Biocatalytic Insights for The Synthesis of New Potential Prodrugs: Design of two Ibuprofen Derivatives |
title_full_unstemmed |
Biocatalytic Insights for The Synthesis of New Potential Prodrugs: Design of two Ibuprofen Derivatives |
title_sort |
biocatalytic insights for the synthesis of new potential prodrugs: design of two ibuprofen derivatives |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2023 |
url |
https://doi.org/10.3390/app13179852 |
op_coverage |
agris |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Applied Sciences Volume 13 Issue 17 Pages: 9852 |
op_relation |
Applied Biosciences and Bioengineering https://dx.doi.org/10.3390/app13179852 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/app13179852 |
container_title |
Applied Sciences |
container_volume |
13 |
container_issue |
17 |
container_start_page |
9852 |
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1778517860759371776 |