TY - JOUR

T1 - Efficient synthesis and evaluation of therapeutic potential of fluorine containing 2-arylchromen-4-ones

AU - Troshkova, Nadezhda

AU - Politanskaya, Larisa

AU - Wang, Jiaying

AU - Niukalova, Maria

AU - Khasanov, Shokhrukh

AU - Esaulkova, Iana

AU - Zarubaev, Vladimir

AU - Boltneva, Natalia

AU - Rudakova, Elena

AU - Kovaleva, Nadezhda

AU - Serebryakova, Olga

AU - Makhaeva, Galina

AU - Valuisky, Nikita

AU - Ibragimova, Umida

AU - Litvinov, Roman

AU - Babkov, Denis

AU - Usenov, Kubanych

AU - Chertenkov, Matvey

AU - Pokrovsky, Mikhail

AU - Cheresiz, Sergey

AU - Pokrovsky, Andrey

N1 - This work was funded by Russian Science Support Foundation, 23-23-00008.

PY - 2025/4

Y1 - 2025/4

N2 - A large series of 2-arylchromen-4-ones containing from 1 to 3 fluorine atoms or a trifluoromethyl group in the structure was synthesized by condensation of fluorinated 2-hydroxyacetophenones with benzaldehydes in an alkaline medium and subsequent oxidative cyclization of the resulting 2’-hydroxychalcones by action of I2 in DMSO. The cytotoxicity of the obtained compounds was studied in glioblastoma cell line, SNB19, and in a monkey-derived normal kidney epithelium cell line, Vero. In addition, antiglycation activity of the obtained compounds was evaluated. The inhibitory activity of some fluorinated 2-arylchromen-4-ones against acetylcholinesterase, butyrylcholinesterase and carboxylesterase as well their primary antioxidant activity in ABTS and FRAP tests were investigated. Screening of the synthesized compounds for their inhibitory activity against influenza A virus A/Puerto Rico/8/34 (H1N1) in the MDCK cell culture revealed that fluorinated compounds 32, 31 and 39 showed manifest antiviral effects (with IS = 57, 38 and 25 correspondingly) that makes this series of new biologically attractive fluorinated heterocycles promising for further development and in-depth study. Graphical abstract: A series of new fluorine-contained 2-aryl-chromen-4-one derivatives were synthesized as potential multi-targets bioactive compounds, among which 32, 31 and 39 were found to be the most promising antiviral agents. (Figure presented.)

AB - A large series of 2-arylchromen-4-ones containing from 1 to 3 fluorine atoms or a trifluoromethyl group in the structure was synthesized by condensation of fluorinated 2-hydroxyacetophenones with benzaldehydes in an alkaline medium and subsequent oxidative cyclization of the resulting 2’-hydroxychalcones by action of I2 in DMSO. The cytotoxicity of the obtained compounds was studied in glioblastoma cell line, SNB19, and in a monkey-derived normal kidney epithelium cell line, Vero. In addition, antiglycation activity of the obtained compounds was evaluated. The inhibitory activity of some fluorinated 2-arylchromen-4-ones against acetylcholinesterase, butyrylcholinesterase and carboxylesterase as well their primary antioxidant activity in ABTS and FRAP tests were investigated. Screening of the synthesized compounds for their inhibitory activity against influenza A virus A/Puerto Rico/8/34 (H1N1) in the MDCK cell culture revealed that fluorinated compounds 32, 31 and 39 showed manifest antiviral effects (with IS = 57, 38 and 25 correspondingly) that makes this series of new biologically attractive fluorinated heterocycles promising for further development and in-depth study. Graphical abstract: A series of new fluorine-contained 2-aryl-chromen-4-one derivatives were synthesized as potential multi-targets bioactive compounds, among which 32, 31 and 39 were found to be the most promising antiviral agents. (Figure presented.)

KW - Anti-glycation activity

KW - Anti-influenza virus activity

KW - Cytotoxicity

KW - Esterase profile

KW - Fluorinated flavones

KW - Chlorocebus aethiops

KW - Antioxidants/pharmacology

KW - Humans

KW - Structure-Activity Relationship

KW - Fluorine/chemistry

KW - Butyrylcholinesterase/metabolism

KW - Animals

KW - Influenza A Virus, H1N1 Subtype/drug effects

KW - Antiviral Agents/pharmacology

KW - Dogs

KW - Halogenation

KW - Madin Darby Canine Kidney Cells

KW - Cell Line, Tumor

KW - Vero Cells

KW - Benzopyrans/chemistry

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85198736110&origin=inward&txGid=d4ccfc673460d88c90f6c05fabe7cbfc

UR - https://www.elibrary.ru/item.asp?id=68864489

UR - https://www.webofscience.com/wos/woscc/full-record/WOS:001269331800001

UR - https://www.mendeley.com/catalogue/a9e19516-c438-30e1-91e5-16cdb3f1a616/

U2 - 10.1007/s11030-024-10925-6

DO - 10.1007/s11030-024-10925-6

M3 - Article

C2 - 39012566

VL - 29

SP - 1427

EP - 1452

JO - Molecular Diversity

JF - Molecular Diversity

SN - 1381-1991

IS - 2

ER -