Direct synthesis of mycophenolic acid aryl esters with antioxidant and antiproliferative properties
Abstract Naturally occurring phenols were incorporated into the mycophenolic acid (MPA) core to form sixteen new MPA derivatives. Ester conjugates of MPA with isoeugenol, methyl o-coumarate, and raspberry ketone exhibited the highest antioxidant activity in the DPPH test. These derivatives were then...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-11871-5 |
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| author | Juliusz Walczak Dorota Iwaszkiewicz-Grześ Magdalena Śliwka-Kaszyńska Agnieszka Kurdyn Ewa Augustin Agnieszka Viapiana Alina Plenis Grzegorz Cholewiński |
| author_facet | Juliusz Walczak Dorota Iwaszkiewicz-Grześ Magdalena Śliwka-Kaszyńska Agnieszka Kurdyn Ewa Augustin Agnieszka Viapiana Alina Plenis Grzegorz Cholewiński |
| author_sort | Juliusz Walczak |
| collection | DOAJ |
| description | Abstract Naturally occurring phenols were incorporated into the mycophenolic acid (MPA) core to form sixteen new MPA derivatives. Ester conjugates of MPA with isoeugenol, methyl o-coumarate, and raspberry ketone exhibited the highest antioxidant activity in the DPPH test. These derivatives were then tested against the human pancreatic cancer AsPC-1 cells, showing cytotoxicity similar to that of the referential parent compounds MPA and mycophenolate mofetil (MMF). Subsequently, most of the obtained MPA esters proved activity against the T-Jurkat cells and peripheral blood mononuclear cells (PBMCs), serving as an immunosuppressive model, and worked as inosine-5’-monophosphate dehydrogenase (IMPDH) inhibitors. The most promising immunosuppressive conjugates were the esters of MPA with sesamol and raspberry ketone structural motifs, which held the highest selectivity index (SI) for PBMCs, thus serving as a good starting point for new drug development. |
| format | Article |
| id | doaj-art-d505fc06761a4d818d54e9461dabdfbc |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-d505fc06761a4d818d54e9461dabdfbc2025-08-20T03:42:38ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-11871-5Direct synthesis of mycophenolic acid aryl esters with antioxidant and antiproliferative propertiesJuliusz Walczak0Dorota Iwaszkiewicz-Grześ1Magdalena Śliwka-Kaszyńska2Agnieszka Kurdyn3Ewa Augustin4Agnieszka Viapiana5Alina Plenis6Grzegorz Cholewiński7Department of Organic Chemistry, Faculty of Chemistry, Gdańsk University of TechnologyDepartment of Medical Immunology, Faculty of Medicine, Medical University of GdanskDepartment of Organic Chemistry, Faculty of Chemistry, Gdańsk University of TechnologyDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdańsk University of TechnologyDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdańsk University of TechnologyDepartment of Analytical Chemistry, Faculty of Pharmacy, Medical University of GdańskDepartment of Analytical Chemistry, Faculty of Pharmacy, Medical University of GdańskDepartment of Organic Chemistry, Faculty of Chemistry, Gdańsk University of TechnologyAbstract Naturally occurring phenols were incorporated into the mycophenolic acid (MPA) core to form sixteen new MPA derivatives. Ester conjugates of MPA with isoeugenol, methyl o-coumarate, and raspberry ketone exhibited the highest antioxidant activity in the DPPH test. These derivatives were then tested against the human pancreatic cancer AsPC-1 cells, showing cytotoxicity similar to that of the referential parent compounds MPA and mycophenolate mofetil (MMF). Subsequently, most of the obtained MPA esters proved activity against the T-Jurkat cells and peripheral blood mononuclear cells (PBMCs), serving as an immunosuppressive model, and worked as inosine-5’-monophosphate dehydrogenase (IMPDH) inhibitors. The most promising immunosuppressive conjugates were the esters of MPA with sesamol and raspberry ketone structural motifs, which held the highest selectivity index (SI) for PBMCs, thus serving as a good starting point for new drug development.https://doi.org/10.1038/s41598-025-11871-5Mycophenolic acidNatural phenolsEsterificationIMPDH inhibitionAntioxidants |
| spellingShingle | Juliusz Walczak Dorota Iwaszkiewicz-Grześ Magdalena Śliwka-Kaszyńska Agnieszka Kurdyn Ewa Augustin Agnieszka Viapiana Alina Plenis Grzegorz Cholewiński Direct synthesis of mycophenolic acid aryl esters with antioxidant and antiproliferative properties Scientific Reports Mycophenolic acid Natural phenols Esterification IMPDH inhibition Antioxidants |
| title | Direct synthesis of mycophenolic acid aryl esters with antioxidant and antiproliferative properties |
| title_full | Direct synthesis of mycophenolic acid aryl esters with antioxidant and antiproliferative properties |
| title_fullStr | Direct synthesis of mycophenolic acid aryl esters with antioxidant and antiproliferative properties |
| title_full_unstemmed | Direct synthesis of mycophenolic acid aryl esters with antioxidant and antiproliferative properties |
| title_short | Direct synthesis of mycophenolic acid aryl esters with antioxidant and antiproliferative properties |
| title_sort | direct synthesis of mycophenolic acid aryl esters with antioxidant and antiproliferative properties |
| topic | Mycophenolic acid Natural phenols Esterification IMPDH inhibition Antioxidants |
| url | https://doi.org/10.1038/s41598-025-11871-5 |
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