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

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Abstract

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.

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Acknowledgements

The authors thank the Multi-Access Chemical Service Center SB RAS for spectral and analytical measurements, and the Russian Science Foundation (Project No. 23-23-00008) for financial support.

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Authors and 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

    Nadezhda Troshkova, Larisa Politanskaya, Irina Bagryanskaya, Igor Chuikov & Jiaying Wang

  2. Novosibirsk State University, Pirogova Street, 2, Novosibirsk, Russian Federation, 630090

    Jiaying Wang

  3. Saint-Petersburg Pasteur Research Institute of Epidemiology and Microbiology, Mira Street, 14, Saint-Petersburg, Russian Federation, 197101

    Polina Ilyina, Mikhail Mikhalski, Iana Esaulkova, Alexandrina Volobueva & Vladimir Zarubaev

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  1. Nadezhda Troshkova
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  2. Larisa Politanskaya
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Contributions

NT: methodology, chemical experiments performing, writing—original draft preparation; LP: conceptualization, methodology, chemical experiments performing, writing—review and editing, funding acquisition, supervision, project administration; IB: RSA investigation, Writing—original draft preparation; IC: NMR investigation, Writing—original draft preparation; JW: chemical experiments performing; PI: biological experiments performing; MM: biological experiments performing; IE: biological experiments performing; AV: biological experiments performing; VZ: methodology, biological experiments performing, writing—review and editing. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Larisa Politanskaya.

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Troshkova, N., Politanskaya, L., Bagryanskaya, I. et al. Fluorinated 2-arylchroman-4-ones and their derivatives: synthesis, structure and antiviral activity. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10769-6

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