Novel O-acylated amidoximes and substituted 1,2,4-oxadiazoles synthesised from (+)-ketopinic acid possessing potent virus-inhibiting activity against phylogenetically distinct influenza A viruses

Novel O-acylated amidoximes and substituted 1,2,4-oxadiazoles synthesised from (+)-ketopinic acid possessing potent virus-inhibiting activity against phylogenetically distinct influenza A viruses Full article

Journal

Bioorganic and Medicinal Chemistry Letters
ISSN: 0960-894X , E-ISSN: 1464-3405

Output data

Year: 2022, Volume: 55, Article number : 128465, Pages count : DOI: 10.1016/j.bmcl.2021.128465

Tags

(+)Ketopinic acid; 1,2,4-oxadiazoles; Antiviral; Influenza virus; Terpene

Authors

Chernyshov Vladimir V. ¹ , Yarovaya Olga I. ¹ , Esaulkova Iana L. ² , Sinegubova Ekaterina ² , Borisevich Sophia S. ³ , Popadyuk Irina I. ¹ , Zarubaev Vladimir V. ² , Salakhutdinov Nariman F. ¹

Affiliations

1	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Lavrent'ev av., 9, Novosibirsk, 630090, Russian Federation
2	Saint-Petersburg Pasteur Institute, 14 Mira str., St. Petersburg, 197101, Russian Federation
3	Ufa Institute of Chemistry, Ufa Federal Research Center, RAS, Octyabrya pr., 71, Ufa, 450054, Russian Federation

This article describes the synthesis and antiviral activity evaluation of new substituted 1,2,4-oxadiazoles containing a bicyclic substituent at position 5 of the heterocycle and O-acylated amidoximes as precursors for their synthesis. New compounds were obtained from the (+)-camphor derivative (+)-ketopinic acid. The chemical library was tested in vitro for cytotoxicity against the MDCK cell line and for antiviral activity against influenza viruses of H1N1 and H7N9 subtypes. The synthesised compounds exhibited high virus-inhibiting activity against the H1N1 influenza virus. Some synthesised compounds were also active against the influenza virus of a different antigenic subtype: H7N9. The mechanism of the virus-inhibiting activity of these compounds is based on their interference with the fusion activity of viral hemagglutinin (HA). No interference with the receptor-binding activity of HA has been demonstrated. According to molecular docking results, the selective antiviral activity of O-acylated amidoximes and 1,2,4-oxadiazoles is associated with their structural features. O-Acylated amidoximes are likely more complementary to the binding site located at the site of the fusion peptide, and 1,2,4-oxadiazoles are more complimentary to the site located at the site of proteolysis. Significant differences in the amino acid residues of the binding sites of HA's of different types allow us to explain the selective antiviral activity of the compounds under study. © 2021 Elsevier Ltd

Chernyshov V.V. , Yarovaya O.I. , Esaulkova I.L. , Sinegubova E. , Borisevich S.S. , Popadyuk I.I. , Zarubaev V.V. , Salakhutdinov N.F.
Novel O-acylated amidoximes and substituted 1,2,4-oxadiazoles synthesised from (+)-ketopinic acid possessing potent virus-inhibiting activity against phylogenetically distinct influenza A viruses
Bioorganic and Medicinal Chemistry Letters. 2022. V.55. 128465 . DOI: 10.1016/j.bmcl.2021.128465 WOS Scopus

Submitted:	Sep 15, 2021
Accepted:	Nov 12, 2021
Published online:	Nov 19, 2021

Web of science	WOS:000722151500007
Scopus	2-s2.0-85120985587
OpenAlex	W3216892025