Biological evaluation of semi-synthetic isoindolinone isomers produced by Stachybotrys chartarum
The filamentous fungus Stachybotrys chartarum is rich in meroterpenoid secondary metabolites, some of which carry o-dialdehyde moieties, which are readily derivatized to isoindolinones by addition of primary amines. The structural diversity of phenylspirodrimanes, in particular, is linked to a wide...
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Fungal Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/ffunb.2024.1494795/full |
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| author | Alica Fischle Alica Fischle Ulrich Schreiber Viola Haupt Felix Schimang Lina Schürmann Matthias Behrens Florian Hübner Melanie Esselen Dmitrii V. Kalinin Svetlana A. Kalinina Svetlana A. Kalinina |
| author_facet | Alica Fischle Alica Fischle Ulrich Schreiber Viola Haupt Felix Schimang Lina Schürmann Matthias Behrens Florian Hübner Melanie Esselen Dmitrii V. Kalinin Svetlana A. Kalinina Svetlana A. Kalinina |
| author_sort | Alica Fischle |
| collection | DOAJ |
| description | The filamentous fungus Stachybotrys chartarum is rich in meroterpenoid secondary metabolites, some of which carry o-dialdehyde moieties, which are readily derivatized to isoindolinones by addition of primary amines. The structural diversity of phenylspirodrimanes, in particular, is linked to a wide range of biological activities, making them ideal candidates for semi-synthetic modification. In this study, acetoxystachybotrydial acetate was reacted with l-tryptophan and tryptamine, resulting in the detection of both regiospecific isomeric structures - a rare and significant finding that enabled the examination of four novel reaction products. Besides their successful purification, a detailed report on their isomer-specific behavior with regard to chromatographic retention, UV-spectral specificities, nuclear magnetic resonances, and mass spectrometric fragmentation is given. Furthermore, a comprehensive insight into each compounds’ unique effect within the tested biological assays is provided, which include cytotoxicity, genotoxicity, their biological activity against serine proteases of the blood coagulation cascade, and in vitro hepatic metabolism, always in comparison to the non-derivatized substance. Ultimately, each isomer can be distinguished already during the purification process, which extends to the biological assays where we present one less cytotoxic, faster metabolized, and more active regio-isomeric phenylspirodrimane-derivative. |
| format | Article |
| id | doaj-art-9e44adf250b04e5cb2f638edf3f50f93 |
| institution | OA Journals |
| issn | 2673-6128 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Fungal Biology |
| spelling | doaj-art-9e44adf250b04e5cb2f638edf3f50f932025-08-20T02:32:48ZengFrontiers Media S.A.Frontiers in Fungal Biology2673-61282024-11-01510.3389/ffunb.2024.14947951494795Biological evaluation of semi-synthetic isoindolinone isomers produced by Stachybotrys chartarumAlica Fischle0Alica Fischle1Ulrich Schreiber2Viola Haupt3Felix Schimang4Lina Schürmann5Matthias Behrens6Florian Hübner7Melanie Esselen8Dmitrii V. Kalinin9Svetlana A. Kalinina10Svetlana A. Kalinina11Instititue of Food Chemistry, University of Münster, Münster, GermanyGraduate School of Natural Products, University of Münster, Münster, GermanyInstititue of Food Chemistry, University of Münster, Münster, GermanyInstititue of Food Chemistry, University of Münster, Münster, GermanyInstititue of Food Chemistry, University of Münster, Münster, GermanyInstititue of Food Chemistry, University of Münster, Münster, GermanyInstititue of Food Chemistry, University of Münster, Münster, GermanyInstititue of Food Chemistry, University of Münster, Münster, GermanyInstititue of Food Chemistry, University of Münster, Münster, GermanyInstitute of Pharmaceutical and Medicinal Chemistry, University of Münster, Münster, GermanyInstititue of Food Chemistry, University of Münster, Münster, GermanyGraduate School of Natural Products, University of Münster, Münster, GermanyThe filamentous fungus Stachybotrys chartarum is rich in meroterpenoid secondary metabolites, some of which carry o-dialdehyde moieties, which are readily derivatized to isoindolinones by addition of primary amines. The structural diversity of phenylspirodrimanes, in particular, is linked to a wide range of biological activities, making them ideal candidates for semi-synthetic modification. In this study, acetoxystachybotrydial acetate was reacted with l-tryptophan and tryptamine, resulting in the detection of both regiospecific isomeric structures - a rare and significant finding that enabled the examination of four novel reaction products. Besides their successful purification, a detailed report on their isomer-specific behavior with regard to chromatographic retention, UV-spectral specificities, nuclear magnetic resonances, and mass spectrometric fragmentation is given. Furthermore, a comprehensive insight into each compounds’ unique effect within the tested biological assays is provided, which include cytotoxicity, genotoxicity, their biological activity against serine proteases of the blood coagulation cascade, and in vitro hepatic metabolism, always in comparison to the non-derivatized substance. Ultimately, each isomer can be distinguished already during the purification process, which extends to the biological assays where we present one less cytotoxic, faster metabolized, and more active regio-isomeric phenylspirodrimane-derivative.https://www.frontiersin.org/articles/10.3389/ffunb.2024.1494795/fullsemi-synthesisregioisomerismStachybotrysgenotoxicitybiological activityhepatic metabolism |
| spellingShingle | Alica Fischle Alica Fischle Ulrich Schreiber Viola Haupt Felix Schimang Lina Schürmann Matthias Behrens Florian Hübner Melanie Esselen Dmitrii V. Kalinin Svetlana A. Kalinina Svetlana A. Kalinina Biological evaluation of semi-synthetic isoindolinone isomers produced by Stachybotrys chartarum Frontiers in Fungal Biology semi-synthesis regioisomerism Stachybotrys genotoxicity biological activity hepatic metabolism |
| title | Biological evaluation of semi-synthetic isoindolinone isomers produced by Stachybotrys chartarum |
| title_full | Biological evaluation of semi-synthetic isoindolinone isomers produced by Stachybotrys chartarum |
| title_fullStr | Biological evaluation of semi-synthetic isoindolinone isomers produced by Stachybotrys chartarum |
| title_full_unstemmed | Biological evaluation of semi-synthetic isoindolinone isomers produced by Stachybotrys chartarum |
| title_short | Biological evaluation of semi-synthetic isoindolinone isomers produced by Stachybotrys chartarum |
| title_sort | biological evaluation of semi synthetic isoindolinone isomers produced by stachybotrys chartarum |
| topic | semi-synthesis regioisomerism Stachybotrys genotoxicity biological activity hepatic metabolism |
| url | https://www.frontiersin.org/articles/10.3389/ffunb.2024.1494795/full |
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