Fluorination of Naturally Occurring N6-Benzyladenosine Remarkably Increased Its Antiviral Activity and Selectivity
Recently, we demonstrated that the natural cytokinin nucleosides N6-isopentenyladenosine (iPR) and N6-benzyladenosine (BAPR) exert a potent and selective antiviral effect on the replication of human enterovirus 71. In order to further characterize the antiviral profile of this class of compounds, we...
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MDPI AG
2017-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/22/7/1219 |
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| author | Vladimir E. Oslovsky Mikhail S. Drenichev Liang Sun Nikolay N. Kurochkin Vladislav E. Kunetsky Carmen Mirabelli Johan Neyts Pieter Leyssen Sergey N. Mikhailov |
| author_facet | Vladimir E. Oslovsky Mikhail S. Drenichev Liang Sun Nikolay N. Kurochkin Vladislav E. Kunetsky Carmen Mirabelli Johan Neyts Pieter Leyssen Sergey N. Mikhailov |
| author_sort | Vladimir E. Oslovsky |
| collection | DOAJ |
| description | Recently, we demonstrated that the natural cytokinin nucleosides N6-isopentenyladenosine (iPR) and N6-benzyladenosine (BAPR) exert a potent and selective antiviral effect on the replication of human enterovirus 71. In order to further characterize the antiviral profile of this class of compounds, we generated a series of fluorinated derivatives of BAPR and evaluated their activity on the replication of human enterovirus 71 in a cytopathic effect (CPE) reduction assay. The monofluorination of the BAPR-phenyl group changed the selectivity index (SI) slightly because of the concomitant high cell toxicity. Interestingly, the incorporation of a second fluorine atom resulted in a dramatic improvement of selectivity. Moreover, N6-trifluoromethylbenzyladenosine derivatives (9–11) exhibited also a very interesting profile, with low cytotoxicity observed. In particular, the analogue N6-(3-trifluoromethylbenzyl)-adenosine (10) with a four-fold gain in potency as compared to BAPR and the best SI in the class represents a promising candidate for further development. |
| first_indexed | 2024-12-22T04:15:26Z |
| format | Article |
| id | doaj.art-d05c342f6a8e4ac1afd1b87b801b61a0 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-22T04:15:26Z |
| publishDate | 2017-07-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-d05c342f6a8e4ac1afd1b87b801b61a02022-12-21T18:39:26ZengMDPI AGMolecules1420-30492017-07-01227121910.3390/molecules22071219molecules22071219Fluorination of Naturally Occurring N6-Benzyladenosine Remarkably Increased Its Antiviral Activity and SelectivityVladimir E. Oslovsky0Mikhail S. Drenichev1Liang Sun2Nikolay N. Kurochkin3Vladislav E. Kunetsky4Carmen Mirabelli5Johan Neyts6Pieter Leyssen7Sergey N. Mikhailov8Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, RussiaLaboratory for Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven-University of Leuven, Minderbroedersstraat 10, Leuven 3000, BelgiumEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, RussiaLaboratory for Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven-University of Leuven, Minderbroedersstraat 10, Leuven 3000, BelgiumLaboratory for Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven-University of Leuven, Minderbroedersstraat 10, Leuven 3000, BelgiumLaboratory for Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven-University of Leuven, Minderbroedersstraat 10, Leuven 3000, BelgiumEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, RussiaRecently, we demonstrated that the natural cytokinin nucleosides N6-isopentenyladenosine (iPR) and N6-benzyladenosine (BAPR) exert a potent and selective antiviral effect on the replication of human enterovirus 71. In order to further characterize the antiviral profile of this class of compounds, we generated a series of fluorinated derivatives of BAPR and evaluated their activity on the replication of human enterovirus 71 in a cytopathic effect (CPE) reduction assay. The monofluorination of the BAPR-phenyl group changed the selectivity index (SI) slightly because of the concomitant high cell toxicity. Interestingly, the incorporation of a second fluorine atom resulted in a dramatic improvement of selectivity. Moreover, N6-trifluoromethylbenzyladenosine derivatives (9–11) exhibited also a very interesting profile, with low cytotoxicity observed. In particular, the analogue N6-(3-trifluoromethylbenzyl)-adenosine (10) with a four-fold gain in potency as compared to BAPR and the best SI in the class represents a promising candidate for further development.https://www.mdpi.com/1420-3049/22/7/1219fluorinated N6-benzyladenosinessynthesis and antiviral activitySARenterovirus 71 |
| spellingShingle | Vladimir E. Oslovsky Mikhail S. Drenichev Liang Sun Nikolay N. Kurochkin Vladislav E. Kunetsky Carmen Mirabelli Johan Neyts Pieter Leyssen Sergey N. Mikhailov Fluorination of Naturally Occurring N6-Benzyladenosine Remarkably Increased Its Antiviral Activity and Selectivity Molecules fluorinated N6-benzyladenosines synthesis and antiviral activity SAR enterovirus 71 |
| title | Fluorination of Naturally Occurring N6-Benzyladenosine Remarkably Increased Its Antiviral Activity and Selectivity |
| title_full | Fluorination of Naturally Occurring N6-Benzyladenosine Remarkably Increased Its Antiviral Activity and Selectivity |
| title_fullStr | Fluorination of Naturally Occurring N6-Benzyladenosine Remarkably Increased Its Antiviral Activity and Selectivity |
| title_full_unstemmed | Fluorination of Naturally Occurring N6-Benzyladenosine Remarkably Increased Its Antiviral Activity and Selectivity |
| title_short | Fluorination of Naturally Occurring N6-Benzyladenosine Remarkably Increased Its Antiviral Activity and Selectivity |
| title_sort | fluorination of naturally occurring n6 benzyladenosine remarkably increased its antiviral activity and selectivity |
| topic | fluorinated N6-benzyladenosines synthesis and antiviral activity SAR enterovirus 71 |
| url | https://www.mdpi.com/1420-3049/22/7/1219 |
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