Design, Synthesis and Antiviral Evaluation of Novel Conjugates of the 1,7,7‐trimethylbicyclo[2.2.1]heptane Scaffold and Saturated N‐heterocycles via 1,2,3‐triazole Linker | Sciact - CRIS-system of Boreskov Institute of Catalysis

Design, Synthesis and Antiviral Evaluation of Novel Conjugates of the 1,7,7‐trimethylbicyclo[2.2.1]heptane Scaffold and Saturated N‐heterocycles via 1,2,3‐triazole Linker Full article

Journal

Archiv der Pharmazie
ISSN: 0365-6233 , E-ISSN: 1521-4184

Output data

Year: 2024, Volume: 357, Number: 3, Article number : e2300549, Pages count : 14 DOI: 10.1002/ardp.202300549

Tags

lysosomotropic compounds, monoterpenoids derivatives, virus inhibitors

Authors

Sokolova Anastasiya S. ¹ , Yarovaya Olga I. ¹ , Artyushin Oleg I. ² , Sharova Elena V. ² , Baev Dmitriy S. ^1,3 , Mordvinova Ekaterina D. ⁴ , Shcherbakov Dmitriy N. ⁴ , Shnaider Tatiana A. ⁵ , Nikitina Tatiana V. ⁶ , Esaulkova Iana L. ⁷ , Ilyina Polina A. ⁷ , Zarubaev Vladimir V. ⁷ , Brel Valery K. ² , Tolstikova Tatyana G. ¹ , Salakhutdinov Nariman F. ¹

Affiliations

1	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russian Federation
2	A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, Russian Federation
3	Synchrotron Radiation Facility SKIF, G.K. Boreskov Institute of Catalysis SB RAS, Koltsovo, Russian Federation
4	State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, Koltsovo, Novosibirsk Region, Russian Federation
5	Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russian Federation
6	Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russian Federation
7	Pasteur Institute of Epidemiology and Microbiology, St. Petersburg, Russian Federation

A new series of heterocyclic derivatives with a 1,7,7-trimethylbicyclo[2.2.1]heptane fragment was designed, synthesised and biologically evaluated. Synthesis of the target compounds was performed using the Cu(I) catalysed cycloaddition reaction. The key starting substances in the click reaction were an alkyne containing a 1,7,7-trimethylbicyclo[2.2.1]heptane fragment and a series of azides with saturated nitrogen-containing heterocycles. Some of the derivatives were found to exhibit strong antiviral activity against Marburg and Ebola pseudotype viruses. Lysosomal trapping assays revealed the derivatives to possess lysosomotropic properties. The molecular modelling study demonstrated the binding affinity between the compounds investigated and the possible active site to be mainly due to hydrophobic interactions. Thus, combining a natural hydrophobic structural fragment and a lysosome-targetable heterocycle may be an effective strategy for designing antiviral agents.

Sokolova A.S. , Yarovaya O.I. , Artyushin O.I. , Sharova E.V. , Baev D.S. , Mordvinova E.D. , Shcherbakov D.N. , Shnaider T.A. , Nikitina T.V. , Esaulkova I.L. , Ilyina P.A. , Zarubaev V.V. , Brel V.K. , Tolstikova T.G. , Salakhutdinov N.F.
Design, Synthesis and Antiviral Evaluation of Novel Conjugates of the 1,7,7‐trimethylbicyclo[2.2.1]heptane Scaffold and Saturated N‐heterocycles via 1,2,3‐triazole Linker
Archiv der Pharmazie. 2024. V.357. N3. e2300549 :1-14. DOI: 10.1002/ardp.202300549 WOS Scopus РИНЦ AN PMID OpenAlex

Submitted:	Sep 29, 2023
Accepted:	Nov 10, 2023
Published online:	Nov 30, 2023
Published print:	Mar 1, 2024

Web of science:	WOS:001111110200001
Scopus:	2-s2.0-85178221033
Elibrary:	64765851
Chemical Abstracts:	2023:2521548
PMID:	38036303
OpenAlex:	W4389208632

DB	Citing
OpenAlex	3
Scopus	1
Web of science	4