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

Twenty-three new quercetin-1,2,3-triazole hybrids were synthesized in good to quantitative yields via Cu(I)-catalyzed azidealkyne 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.

Automated summary

Twenty-three new quercetin-1,2,3-triazole hybrids were synthesized and showed potent antiproliferative activity against canine mammary cancer cells.