TY - JOUR

T1 - Fluorinated 2-arylchroman-4-ones and their derivatives: synthesis, structure and antiviral activity

AU - Troshkova, Nadezhda

AU - Politanskaya, Larisa

AU - Bagryanskaya, Irina

AU - Chuikov, Igor

AU - Wang, Jiaying

AU - Ilyina, Polina

AU - Mikhalski, Mikhail

AU - Esaulkova, Iana

AU - Volobueva, Alexandrina

AU - Zarubaev, Vladimir

N1 - 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. © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - 4,5-Diaryl-4H,5H-pyrano[3,2-c]chromenes

KW - Anti-viral activity

KW - Cycloaddition

KW - Fluorinated flavanones

KW - Influenza virus

KW - p-Toluenesulfonic acid

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85180658523&origin=inward&txGid=97ebff90ccec344f599d88c4ed3ec1e5

UR - https://www.mendeley.com/catalogue/4e0f8e1c-0ad6-36e6-b541-73f24c06ebdf/

U2 - 10.1007/s11030-023-10769-6

DO - 10.1007/s11030-023-10769-6

M3 - Article

C2 - 38153637

JO - Molecular Diversity

JF - Molecular Diversity

SN - 1381-1991

ER -