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Synthesis 2022; 54(19): 4272-4284
DOI: 10.1055/s-0040-1719928
special topic
SYNTHESIS Conference Special Topic ISySyCat21

Synthesis and Antiproliferative Activity of Novel Quercetin-1,2,3-Triazole Hybrids using the 1,3-Dipolar Cycloaddition (Click) Reaction

Elisabete P. Carreiro  ∗
a   University of Évora, Institute of Research and Advanced Training, LAQV-REQUIMTE, Rua Romão Ramalho, 59, 7000-671 Évora, Portugal
,
Carlos M. Gastalho 
b   University of Évora, School of Science and Technology, Department of Chemistry and Biochemistry, Rua Romão Ramalho, 59, 7000-671 Évora, Portugal
c   University of Évora, School of Health and Human Development, Department of Medical and Health Sciences, Rua Romão Ramalho, 59, 7000-671 Évora, Portugal
,
Sofia Ernesto
b   University of Évora, School of Science and Technology, Department of Chemistry and Biochemistry, Rua Romão Ramalho, 59, 7000-671 Évora, Portugal
,
Ana R. Costa
c   University of Évora, School of Health and Human Development, Department of Medical and Health Sciences, Rua Romão Ramalho, 59, 7000-671 Évora, Portugal
d   University of Évora, Institute of Research and Advanced Training, Institute of Earth Sciences, Rua Romao Ramalho, 59, 7000-671 Evora, Portugal
,
Célia M. Antunes
c   University of Évora, School of Health and Human Development, Department of Medical and Health Sciences, Rua Romão Ramalho, 59, 7000-671 Évora, Portugal
d   University of Évora, Institute of Research and Advanced Training, Institute of Earth Sciences, Rua Romao Ramalho, 59, 7000-671 Evora, Portugal
,
Anthony J. Burke 
a   University of Évora, Institute of Research and Advanced Training, LAQV-REQUIMTE, Rua Romão Ramalho, 59, 7000-671 Évora, Portugal
b   University of Évora, School of Science and Technology, Department of Chemistry and Biochemistry, Rua Romão Ramalho, 59, 7000-671 Évora, Portugal
› Author Affiliations The work was supported through the project UIDB/50006/2020 | UIDP/50006/2020, funded by Fundação para a Ciência e Tecnologia (FCT)/ Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through national funds.
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Abstract

Twenty-three new quercetin-1,2,3-triazole hybrids were synthesized in good to quantitative yields via Cu(I)-catalyzed azide-alkyne cycloaddition reaction under microwave irradiation. These new hybrids contain a 1,4-disubstituted 1,2,3-triazole ring at the 3-OH position of quercetin whilst the remaining hydroxyl groups were either protected as methyl or benzyl groups or left unprotected. All the quercetin-1,2,3-triazole hybrids I–IV were evaluated against REM-134 canine mammary cancer cell line, which is used as a translational model for human breast cancer. These new analogues exhibit potent antiproliferative activity against this cancer cell line. Furthermore, the results show that some of the new quercetin-1,2,3-triazole hybrids have better activity than quercetin. Our best inhibitors displayed IC50 values in the range of 41–180 nM, and undoubtedly will have an important impact on the treatment of both canine and human breast cancer.

Key words

quercetin - 1,2,3-triazole - Huisgen reaction - molecular hybridization - anticancer - flavonoid

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1719928.
  • Supporting Information


Publication History

Received: 16 February 2022

Accepted after revision: 22 April 2022

Article published online:
08 June 2022

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