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3-[N,N-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-[N,N-bis(sulfonyl)amino]isoxazolines containing spiro-annulated cyclooctane rings and assessed their antivira...

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Autores principales: Sedenkova, Kseniya N., Sazonov, Artem S., Vasilenko, Dmitry A., Andriasov, Kristian S., Eremenko, Marina G., Grishin, Yuri K., Khvatov, Evgeny V., Goryashchenko, Alexander S., Uvarova, Victoria I., Osolodkin, Dmitry I., Ishmukhametov, Aydar A., Averina, Elena B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341786/
https://www.ncbi.nlm.nih.gov/pubmed/37445937
http://dx.doi.org/10.3390/ijms241310758
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author Sedenkova, Kseniya N.
Sazonov, Artem S.
Vasilenko, Dmitry A.
Andriasov, Kristian S.
Eremenko, Marina G.
Grishin, Yuri K.
Khvatov, Evgeny V.
Goryashchenko, Alexander S.
Uvarova, Victoria I.
Osolodkin, Dmitry I.
Ishmukhametov, Aydar A.
Averina, Elena B.
author_facet Sedenkova, Kseniya N.
Sazonov, Artem S.
Vasilenko, Dmitry A.
Andriasov, Kristian S.
Eremenko, Marina G.
Grishin, Yuri K.
Khvatov, Evgeny V.
Goryashchenko, Alexander S.
Uvarova, Victoria I.
Osolodkin, Dmitry I.
Ishmukhametov, Aydar A.
Averina, Elena B.
author_sort Sedenkova, Kseniya N.
collection PubMed
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-[N,N-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-[N,N-bis(sulfonyl)amino]isoxazolines revealed antiviral activity against TBEV and WNV. The most active against TBEV was spiro-isoxazoline derivative containing p-nitrophenyl groups in the sulfonyl part (EC(50) 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(50) 1.3 ± 0.5 μM). In summary, two novel scaffolds of anti-flaviviral agents based on N,N-bis(sulfonyl)amino]isoxazoline were proposed, and the compounds of this type demonstrated activity against TBEV and WNV.
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spelling pubmed-103417862023-07-14 3-[N,N-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 Sedenkova, Kseniya N. Sazonov, Artem S. Vasilenko, Dmitry A. Andriasov, Kristian S. Eremenko, Marina G. Grishin, Yuri K. Khvatov, Evgeny V. Goryashchenko, Alexander S. Uvarova, Victoria I. Osolodkin, Dmitry I. Ishmukhametov, Aydar A. Averina, Elena B. Int J Mol Sci Article 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-[N,N-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-[N,N-bis(sulfonyl)amino]isoxazolines revealed antiviral activity against TBEV and WNV. The most active against TBEV was spiro-isoxazoline derivative containing p-nitrophenyl groups in the sulfonyl part (EC(50) 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(50) 1.3 ± 0.5 μM). In summary, two novel scaffolds of anti-flaviviral agents based on N,N-bis(sulfonyl)amino]isoxazoline were proposed, and the compounds of this type demonstrated activity against TBEV and WNV. MDPI 2023-06-28 /pmc/articles/PMC10341786/ /pubmed/37445937 http://dx.doi.org/10.3390/ijms241310758 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sedenkova, Kseniya N.
Sazonov, Artem S.
Vasilenko, Dmitry A.
Andriasov, Kristian S.
Eremenko, Marina G.
Grishin, Yuri K.
Khvatov, Evgeny V.
Goryashchenko, Alexander S.
Uvarova, Victoria I.
Osolodkin, Dmitry I.
Ishmukhametov, Aydar A.
Averina, Elena B.
3-[N,N-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 3-[N,N-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-[N,N-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-[N,N-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-[N,N-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-[N,N-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-[n,n-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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341786/
https://www.ncbi.nlm.nih.gov/pubmed/37445937
http://dx.doi.org/10.3390/ijms241310758
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