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DOI: 10.1055/s-0040-1719928
Synthesis and Antiproliferative Activity of Novel Quercetin-1,2,3-Triazole Hybrids using the 1,3-Dipolar Cycloaddition (Click) Reaction
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.
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 - flavonoidSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1719928.
- Supporting Information
Publikationsverlauf
Eingereicht: 16. Februar 2022
Angenommen nach Revision: 22. April 2022
Artikel online veröffentlicht:
08. Juni 2022
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References
- 1 Current address: Faculty of Pharmacy University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
- 2a Tang S.-M, Deng X.-T, Zhou J, Li Q.-P, Ge X.-X, Miao L. Biomed. Pharmacother. 2020; 121: 109604
- 2b Batiha GE.-S, Beshbishy AM, Ikram M, Mulla ZS, El-Hack ME. A, Taha AE, Algammal AM, Elewa YH. A. Foods 2020; 9: 374
- 3a Massi A, Bortolini O, Ragno D, Bernardi T, Sacchetti G, Tacchini M, De Risi C. Molecules 2017; 22: 1270
- 3b Dobrydnev AV, Tkachuk TM, Atamaniuk VP, Popova MV. Mini-Rev. Med. Chem. 2020; 20: 107
- 3c Alizadeh SR, Ebrahimzadeh MA. J. Mol. Struct. 2022; 1254: 13239 ; and citations therein
- 4a Wang R, Yang L, Li S, Ye D, Yang L, Liu Q, Zhao Z, Cai Q, Tan J, Li X. Med. Sci. Monit. 2018; 24: 412
- 4b Ezzati M, Yousefi B, Velaei K, Safa A. Life Sci. 2020; 248: 117463 ; and citations therein
- 4c Lewinska A, Przybylski P, Adamczyk-Grochala J, Błoniarz D, Litwinienko G, Wnuk M. Cancers 2022; 14: 605
- 5a Dheer D, Singh V, Shankar R. Bioorg. Chem. 2017; 71: 30 ; and citations therein
- 5b Bozorov K, Zhao J, Aisa HA. Bioorg. Med. Chem. 2019; 27: 3511 ; and citations therein
- 6a Xu Z, Zhao S.-J, Liu Y. Eur. J. Med. Chem. 2019; 183: 1117002 ; and citations therein
- 6b Alam MM. Arch. Pharm. 2021; 355: 2100158 ; and citations therein
- 7a Carreiro EP, Sena AM, Puerta A, Padrón JM, Burke AJ. Synlett 2020; 31: 615
- 7b Barrulas P, Carreiro EP, Veiros LF, Amorim AC, Gut G, Rosenthal P, López O, Puerta A, Padrón JM, Fernandez-Bolanos JG, Burke AJ. Synth. Commun. 2021; 51: 2954
- 7c Marques CS, Busto N, Gaudio E, Bertoni F, Burke AJ. EP3400938, 2018
- 8a Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. Angew. Chem. Int. Ed. 2002; 41: 2596
- 8b Tornoe C, Christensen C, Meldal M. J. Org. Chem. 2002; 67: 3057
- 8c Mashayekh K, Shiri P. ChemistrySelect 2019; 4: 13459
- 9 Bérubé G. Expert Opin. Drug Discovery 2016; 11: 281
- 10a Guo H.-Y, Chen Z.-A, Shen Q.-K, Quan Z.-S. J. Enzyme Inhib. Med. Chem. 2021; 36: 1115
- 10b Bian J, Ren J, Li Y, Wang J, Xu X, Feng Y, Tang H, Wang Y, Li Z. Bioorg. Chem. 2018; 81: 373
- 10c Qi Y, Ding Z, Yao Y, Ma D, Ren F, Yang H, Chen A. Exp. Ther. Med. 2019; 17: 1670
- 10d Noole V, Krishna T, Godeshala S, Meraji S, Rege K, Reddy CK, Kedika B. Anti-Cancer Agents Med. Chem. 2022; 22: 160
- 10e Pereira D, Pinto M, Correia-da-Silva M, Cidade H. Molecules 2022; 27: 230
- 11 Wang G.-Q, Yan L.-L, Wang Q.-A. Heterocycl. Commun. 2018; 24: 119
- 12 Gray M, Meehan J, Martínez-Pérez C, Kay C, Turnbull AK, Morrison LR, Pang LY, Argyle D. Front. Oncol. 2020; 10: 617
- 13a Lu K, Yang K, Jia X, Gao X, Zhao X, Pan G, Ma Y, Huang Q, Yu P. Org. Chem. Front. 2017; 4: 578
- 13b Kajjout M, Zemmouri R, Rolando C. Tetrahedron Lett. 2011; 52: 4738
- 14 González-Olvera R, Román-Rodríguez V, Negrón-Silva GE, Espinoza-Vázquez A, Rodríguez-Gómez FJ, Santillan R. Molecules 2016; 21: 250
- 15 Yu B, Qi P.-P, Shi X.-J, Huang R, Guo H, Zheng Y.-C, Yu D.-Q, Liu H.-M. Eur. J. Med. Chem. 2016; 117: 241
- 16 Alam MM, Malebari AM, Nazreena S, Neamatallah T, Almalkid AS. A, Elhenawy AA, Obaid RJ, Alsharif MA. Bioorg. Med. Chem. 2021; 38: 116136