Synthesis, H2S releasing properties, antiviral and antioxidant activities and acute cardiac effects of nucleoside 5′-dithioacetates
Abstract Hydrogen sulfide (H2S) is an endogenous gasotransmitter with cardioprotective and antiviral effects. In this work, new cysteine-selective nucleoside-H2S-donor hybrid molecules were prepared by conjugating nucleoside biomolecules with a thiol-activatable dithioacetyl group. 5′-Dithioacetate...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-85351-1 |
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| author | Miklós Bege Miklós Lovas Dániel Priksz Brigitta Bernát Ilona Bereczki Rasha Ghanem Kattoub Richárd Kajtár Simon Eskeif Levente Novák Jan Hodek Jan Weber Pál Herczegh István Lekli Anikó Borbás |
| author_facet | Miklós Bege Miklós Lovas Dániel Priksz Brigitta Bernát Ilona Bereczki Rasha Ghanem Kattoub Richárd Kajtár Simon Eskeif Levente Novák Jan Hodek Jan Weber Pál Herczegh István Lekli Anikó Borbás |
| author_sort | Miklós Bege |
| collection | DOAJ |
| description | Abstract Hydrogen sulfide (H2S) is an endogenous gasotransmitter with cardioprotective and antiviral effects. In this work, new cysteine-selective nucleoside-H2S-donor hybrid molecules were prepared by conjugating nucleoside biomolecules with a thiol-activatable dithioacetyl group. 5′-Dithioacetate derivatives were synthesized from the canonical nucleosides (uridine, adenosine, cytidine, guanosine and thymidine), and the putative 5′-thio metabolites were also produced from uridine and adenosine. According to our measurements made with an H2S-specific sensor, nucleoside dithioacetates are moderately fast H2S donors, the guanosine derivative showed the fastest kinetics and the adenosine derivative the slowest. The antioxidant activity of 5′-thionucleosides is significantly higher than that of trolox, but lower than that of ascorbic acid, while intact dithioacetates have no remarkable antioxidant effect. In human Calu cells, the guanosine derivative showed a moderate anti-SARS-CoV-2 effect which was also confirmed by virus yield reduction assay. Dithioacetyl-adenosine and its metabolite showed similar acute cardiac effects as adenosine, however, it is noteworthy that both 5′-thio modified adenosines increased left ventricular ejection fraction or stroke volume, which was not observed with native adenosine. |
| format | Article |
| id | doaj-art-fed703721a7542749b16a78e88290851 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-fed703721a7542749b16a78e882908512025-01-26T12:30:47ZengNature PortfolioScientific Reports2045-23222025-01-0115111910.1038/s41598-025-85351-1Synthesis, H2S releasing properties, antiviral and antioxidant activities and acute cardiac effects of nucleoside 5′-dithioacetatesMiklós Bege0Miklós Lovas1Dániel Priksz2Brigitta Bernát3Ilona Bereczki4Rasha Ghanem Kattoub5Richárd Kajtár6Simon Eskeif7Levente Novák8Jan Hodek9Jan Weber10Pál Herczegh11István Lekli12Anikó Borbás13Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of DebrecenDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of DebrecenDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of DebrecenDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of DebrecenDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of DebrecenDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of DebrecenDoctoral School of Pharmaceutical Sciences, Faculty of Pharmacy, University of DebrecenDoctoral School of Pharmaceutical Sciences, Faculty of Pharmacy, University of DebrecenDepartment of Physical Chemistry, Faculty of Science and Technology, University of DebrecenInstitute of Organic Chemistry and Biochemistry, Czech Academy of SciencesInstitute of Organic Chemistry and Biochemistry, Czech Academy of SciencesDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of DebrecenDepartment of Pharmacodynamics, Faculty of Pharmacy, University of DebrecenDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of DebrecenAbstract Hydrogen sulfide (H2S) is an endogenous gasotransmitter with cardioprotective and antiviral effects. In this work, new cysteine-selective nucleoside-H2S-donor hybrid molecules were prepared by conjugating nucleoside biomolecules with a thiol-activatable dithioacetyl group. 5′-Dithioacetate derivatives were synthesized from the canonical nucleosides (uridine, adenosine, cytidine, guanosine and thymidine), and the putative 5′-thio metabolites were also produced from uridine and adenosine. According to our measurements made with an H2S-specific sensor, nucleoside dithioacetates are moderately fast H2S donors, the guanosine derivative showed the fastest kinetics and the adenosine derivative the slowest. The antioxidant activity of 5′-thionucleosides is significantly higher than that of trolox, but lower than that of ascorbic acid, while intact dithioacetates have no remarkable antioxidant effect. In human Calu cells, the guanosine derivative showed a moderate anti-SARS-CoV-2 effect which was also confirmed by virus yield reduction assay. Dithioacetyl-adenosine and its metabolite showed similar acute cardiac effects as adenosine, however, it is noteworthy that both 5′-thio modified adenosines increased left ventricular ejection fraction or stroke volume, which was not observed with native adenosine.https://doi.org/10.1038/s41598-025-85351-1NucleosideDithioacetateH2S donorH2S release kineticsAntioxidantAntiviral |
| spellingShingle | Miklós Bege Miklós Lovas Dániel Priksz Brigitta Bernát Ilona Bereczki Rasha Ghanem Kattoub Richárd Kajtár Simon Eskeif Levente Novák Jan Hodek Jan Weber Pál Herczegh István Lekli Anikó Borbás Synthesis, H2S releasing properties, antiviral and antioxidant activities and acute cardiac effects of nucleoside 5′-dithioacetates Scientific Reports Nucleoside Dithioacetate H2S donor H2S release kinetics Antioxidant Antiviral |
| title | Synthesis, H2S releasing properties, antiviral and antioxidant activities and acute cardiac effects of nucleoside 5′-dithioacetates |
| title_full | Synthesis, H2S releasing properties, antiviral and antioxidant activities and acute cardiac effects of nucleoside 5′-dithioacetates |
| title_fullStr | Synthesis, H2S releasing properties, antiviral and antioxidant activities and acute cardiac effects of nucleoside 5′-dithioacetates |
| title_full_unstemmed | Synthesis, H2S releasing properties, antiviral and antioxidant activities and acute cardiac effects of nucleoside 5′-dithioacetates |
| title_short | Synthesis, H2S releasing properties, antiviral and antioxidant activities and acute cardiac effects of nucleoside 5′-dithioacetates |
| title_sort | synthesis h2s releasing properties antiviral and antioxidant activities and acute cardiac effects of nucleoside 5 dithioacetates |
| topic | Nucleoside Dithioacetate H2S donor H2S release kinetics Antioxidant Antiviral |
| url | https://doi.org/10.1038/s41598-025-85351-1 |
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