Synthesis and antiviral activity of formycin derivatives with anti-influenza virus activity
[Display omitted] In a screening using our unique natural product library, the C-nucleoside antibiotic formycin A, which exerts strong anti-influenza virus activity, was rediscovered. Aiming to develop a new type of anti-influenza virus drug, we synthesized new derivatives of formycin and evaluated...
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| Published in: | Bioorganic & medicinal chemistry Vol. 57; p. 116613 |
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| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
Elsevier Ltd
01-03-2022
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | [Display omitted]
In a screening using our unique natural product library, the C-nucleoside antibiotic formycin A, which exerts strong anti-influenza virus activity, was rediscovered. Aiming to develop a new type of anti-influenza virus drug, we synthesized new derivatives of formycin and evaluated its anti-influenza virus activity. Structural modifications were focused on the base moiety and sugar portion, respectively, and >40 novel formycin derivatives were synthesized. Modification of the C-7 position of the pyrazolopyrimidine ring strongly contributed to improve the activity. In particular, excellent anti-influenza virus activity was observed in the NHMe (10), SMe (12), and SeMe (15) derivatives, in which heteroatoms were introduced. In addition, in the modification of the sugar moiety, the presence of a hydroxyl group and its stereochemistry greatly affected both the expression and intensity of the activity. Furthermore, the evaluation results of the 7-SEt derivative (29) and the 2′-modified derivative (59) suggested that structural modifications may reduce cytotoxicity. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0968-0896 1464-3391 |
| DOI: | 10.1016/j.bmc.2022.116613 |