Fluorinated 2‑arylchroman‑4‑ones and their derivatives: synthesis, structure and antiviral activity

Fluorinated 2‑arylchroman‑4‑ones and their derivatives: synthesis, structure and antiviral activity Full article

Journal

Molecular Diversity
ISSN: 1381-1991 , E-ISSN: 1573-501X

Output data

Year: 2024, Volume: 28, Number: 6, Pages: 3635–3660 Pages count : DOI: 10.1007/s11030-023-10769-6

Tags

Fluorinated flavanones 4,5-Diaryl-4H,5H-pyrano[3,2-c]chromenes Cycloaddition p-Toluenesulfonic acid Anti-viral activity Influenza virus

Authors

Troshkova Nadezhda ¹ , Politanskaya Larisa ¹ , Bagryanskaya Irina ¹ , Chuikov Igor ¹ , Wang Jiaying ^1,2 , Ilyina Polina ³ , Mikhalski Mikhail ³ , Esaulkova Iana ³ , Volobueva Alexandrina ³ , Zarubaev Vladimir ³

Affiliations

1	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, Ac. Lavrentiev Avenue, 9, Novosibirsk, Russian Federation, 630090
2	Novosibirsk State University, Pirogova Street, 2, Novosibirsk, Russian Federation, 630090
3	Saint-Petersburg Pasteur Research Institute of Epidemiology and Microbiology, Mira Street, 14, Saint-Petersburg, Russian Federation, 197101

Funding (1)

Российский Научный Фонд

23-23-00008

A number of new biologically interesting fluorinated 2-arylchroman-4-ones and their 3-arylidene derivatives were synthesized based on the p-toluenesulfonic acid-catalyzed one-pot reaction of 2-hydroxyacetophenones with benzaldehydes. It was found that obtained (E)-3-arylidene-2-aryl-chroman-4-ones reacted with malononitrile under base conditions to form 4,5-diaryl-4H,5H-pyrano[3,2-c]chromenes. The structures of the synthesized fluorinated compounds were confirmed by 1H, 19F, and 13C NMR spectral data, and for some representatives of heterocycles also using NOESY spectra and X-ray diffraction analysis. A large series of obtained flavanone derivatives as well as products of their modification (35 examples) containing from 1 to 12 fluorine atoms in the structure was tested in vitro for cytotoxicity in MDCK cell line and for antiviral activity against influenza A virus. Among the studied heterocycles 6,8-difluoro-2-(4-(trifluoromethyl)phenyl)chroman-4-one (IC50 = 6 μM, SI = 150) exhibited the greatest activity against influenza A/Puerto Rico/8/34 (H1N1) virus. Moreover, this compound appeared active against phylogenetically distinct influenza viruses, A(H5N2) and influenza B (SI’s of 53 and 42, correspondingly). The data obtained suggest that the fluorinated derivatives of 2-arylchroman-4-ones are prospective scaffolds for further development of potent anti-influenza antivirals.

Troshkova N. , Politanskaya L. , Bagryanskaya I. , Chuikov I. , Wang J. , Ilyina P. , Mikhalski M. , Esaulkova I. , Volobueva A. , Zarubaev V.
Fluorinated 2‑arylchroman‑4‑ones and their derivatives: synthesis, structure and antiviral activity
Molecular Diversity. 2024. V.28. N6. P.3635–3660. DOI: 10.1007/s11030-023-10769-6 WOS Scopus РИНЦ OpenAlex

Submitted:	Sep 21, 2023
Accepted:	Nov 10, 2023
Published online:	Dec 28, 2023
Published print:	Dec 1, 2024

Web of science:	WOS:001132381600001
Scopus:	2-s2.0-85180658523
Elibrary:	64660937
OpenAlex:	W4390345683

DB	Citing
OpenAlex	5
Web of science	3