3-[<i>N,N</i>-Bis(sulfonyl)amino]isoxazolines with Spiro-Annulated or 1,2-Annulated Cyclooctane Rings Inhibit Reproduction of Tick-Borne Encephalitis, Yellow Fever, and West Nile Viruses
Spirocyclic compounds containing heterocyclic moieties represent promising 3D scaffolds for modern drug design. In the search for novel anti-flaviviral agents, we have obtained a series of 3-[<i>N,N</i>-bis(sulfonyl)amino]isoxazolines containing spiro-annulated cyclooctane rings and asse...
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| Format: | Article |
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2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| author | Kseniya N. Sedenkova Artem S. Sazonov Dmitry A. Vasilenko Kristian S. Andriasov Marina G. Eremenko Yuri K. Grishin Evgeny V. Khvatov Alexander S. Goryashchenko Victoria I. Uvarova Dmitry I. Osolodkin Aydar A. Ishmukhametov Elena B. Averina |
| author_facet | Kseniya N. Sedenkova Artem S. Sazonov Dmitry A. Vasilenko Kristian S. Andriasov Marina G. Eremenko Yuri K. Grishin Evgeny V. Khvatov Alexander S. Goryashchenko Victoria I. Uvarova Dmitry I. Osolodkin Aydar A. Ishmukhametov Elena B. Averina |
| author_sort | Kseniya N. Sedenkova |
| collection | DOAJ |
| description | Spirocyclic compounds containing heterocyclic moieties represent promising 3D scaffolds for modern drug design. In the search for novel anti-flaviviral agents, we have obtained a series of 3-[<i>N,N</i>-bis(sulfonyl)amino]isoxazolines containing spiro-annulated cyclooctane rings and assessed their antiviral activity against tick-borne encephalitis (TBEV), yellow fever (YFV), and West Nile (WNV) viruses. The structural analogs of spirocyclic compounds with a single sulfonyl group or 1,2-annulated cyclooctane ring were also investigated. Almost all the studied 3-[<i>N,N</i>-bis(sulfonyl)amino]isoxazolines revealed antiviral activity against TBEV and WNV. The most active against TBEV was spiro-isoxazoline derivative containing <i>p</i>-nitrophenyl groups in the sulfonyl part (EC<sub>50</sub> 2.0 ± 0.5 μM), while the highest potency against WNV was found for the compounds with lipophilic substituents in sulfonyl moiety, naphtyl being the most favorable one (EC<sub>50</sub> 1.3 ± 0.5 μM). In summary, two novel scaffolds of anti-flaviviral agents based on <i>N,N</i>-bis(sulfonyl)amino]isoxazoline were proposed, and the compounds of this type demonstrated activity against TBEV and WNV. |
| first_indexed | 2024-03-11T01:38:47Z |
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| id | doaj.art-1abd5c01074f4c61b5fa0d5b30ff0041 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:38:47Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1abd5c01074f4c61b5fa0d5b30ff00412023-11-18T16:43:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131075810.3390/ijms2413107583-[<i>N,N</i>-Bis(sulfonyl)amino]isoxazolines with Spiro-Annulated or 1,2-Annulated Cyclooctane Rings Inhibit Reproduction of Tick-Borne Encephalitis, Yellow Fever, and West Nile VirusesKseniya N. Sedenkova0Artem S. Sazonov1Dmitry A. Vasilenko2Kristian S. Andriasov3Marina G. Eremenko4Yuri K. Grishin5Evgeny V. Khvatov6Alexander S. Goryashchenko7Victoria I. Uvarova8Dmitry I. Osolodkin9Aydar A. Ishmukhametov10Elena B. Averina11Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Moscow 119991, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Moscow 119991, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Moscow 119991, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Moscow 119991, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Moscow 119991, RussiaFSASI “Chumakov FSC R&D IBP RAS” (Institute of Poliomyelitis), Moscow 108819, RussiaFSASI “Chumakov FSC R&D IBP RAS” (Institute of Poliomyelitis), Moscow 108819, RussiaFSASI “Chumakov FSC R&D IBP RAS” (Institute of Poliomyelitis), Moscow 108819, RussiaFSASI “Chumakov FSC R&D IBP RAS” (Institute of Poliomyelitis), Moscow 108819, RussiaFSASI “Chumakov FSC R&D IBP RAS” (Institute of Poliomyelitis), Moscow 108819, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Moscow 119991, RussiaSpirocyclic compounds containing heterocyclic moieties represent promising 3D scaffolds for modern drug design. In the search for novel anti-flaviviral agents, we have obtained a series of 3-[<i>N,N</i>-bis(sulfonyl)amino]isoxazolines containing spiro-annulated cyclooctane rings and assessed their antiviral activity against tick-borne encephalitis (TBEV), yellow fever (YFV), and West Nile (WNV) viruses. The structural analogs of spirocyclic compounds with a single sulfonyl group or 1,2-annulated cyclooctane ring were also investigated. Almost all the studied 3-[<i>N,N</i>-bis(sulfonyl)amino]isoxazolines revealed antiviral activity against TBEV and WNV. The most active against TBEV was spiro-isoxazoline derivative containing <i>p</i>-nitrophenyl groups in the sulfonyl part (EC<sub>50</sub> 2.0 ± 0.5 μM), while the highest potency against WNV was found for the compounds with lipophilic substituents in sulfonyl moiety, naphtyl being the most favorable one (EC<sub>50</sub> 1.3 ± 0.5 μM). In summary, two novel scaffolds of anti-flaviviral agents based on <i>N,N</i>-bis(sulfonyl)amino]isoxazoline were proposed, and the compounds of this type demonstrated activity against TBEV and WNV.https://www.mdpi.com/1422-0067/24/13/10758tick-borne encephalitis virusyellow fever virusWest Nile virusantiviralsisoxazolinesspiro-compounds |
| spellingShingle | Kseniya N. Sedenkova Artem S. Sazonov Dmitry A. Vasilenko Kristian S. Andriasov Marina G. Eremenko Yuri K. Grishin Evgeny V. Khvatov Alexander S. Goryashchenko Victoria I. Uvarova Dmitry I. Osolodkin Aydar A. Ishmukhametov Elena B. Averina 3-[<i>N,N</i>-Bis(sulfonyl)amino]isoxazolines with Spiro-Annulated or 1,2-Annulated Cyclooctane Rings Inhibit Reproduction of Tick-Borne Encephalitis, Yellow Fever, and West Nile Viruses International Journal of Molecular Sciences tick-borne encephalitis virus yellow fever virus West Nile virus antivirals isoxazolines spiro-compounds |
| title | 3-[<i>N,N</i>-Bis(sulfonyl)amino]isoxazolines with Spiro-Annulated or 1,2-Annulated Cyclooctane Rings Inhibit Reproduction of Tick-Borne Encephalitis, Yellow Fever, and West Nile Viruses |
| title_full | 3-[<i>N,N</i>-Bis(sulfonyl)amino]isoxazolines with Spiro-Annulated or 1,2-Annulated Cyclooctane Rings Inhibit Reproduction of Tick-Borne Encephalitis, Yellow Fever, and West Nile Viruses |
| title_fullStr | 3-[<i>N,N</i>-Bis(sulfonyl)amino]isoxazolines with Spiro-Annulated or 1,2-Annulated Cyclooctane Rings Inhibit Reproduction of Tick-Borne Encephalitis, Yellow Fever, and West Nile Viruses |
| title_full_unstemmed | 3-[<i>N,N</i>-Bis(sulfonyl)amino]isoxazolines with Spiro-Annulated or 1,2-Annulated Cyclooctane Rings Inhibit Reproduction of Tick-Borne Encephalitis, Yellow Fever, and West Nile Viruses |
| title_short | 3-[<i>N,N</i>-Bis(sulfonyl)amino]isoxazolines with Spiro-Annulated or 1,2-Annulated Cyclooctane Rings Inhibit Reproduction of Tick-Borne Encephalitis, Yellow Fever, and West Nile Viruses |
| title_sort | 3 i n n i bis sulfonyl amino isoxazolines with spiro annulated or 1 2 annulated cyclooctane rings inhibit reproduction of tick borne encephalitis yellow fever and west nile viruses |
| topic | tick-borne encephalitis virus yellow fever virus West Nile virus antivirals isoxazolines spiro-compounds |
| url | https://www.mdpi.com/1422-0067/24/13/10758 |
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