Novel Quercetin-1,2,3- Triazole Hybrids using the 1,3-Dipolar Cycloaddition (Click) Reaction: synthesis and antiproliferative activity assays

Quercetin is a polyphenolic flavonoid with recognized strong antioxidant potential, which can prevent and treat several diseases. Hybrids containing a heterocyclic 1,2,3-triazole have shown promising biological properties, such as anticancer, anti-Alzheimer’s, among others. The hybridization of these two entities can allow the discovery of new molecules with more potent biological properties.

Novel quercetin-1,2,3-triazole hybrids were prepared in good to excelent 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 tested on REM-134 canine mammary cancer cell line, which is commonly used as a translational model for human breast cancer. These new analogues exhibit potent antiproliferative activity against this cancer cell line. The results show that some of these new quercetin-1,2,3-triazole hybrids have better activity than quercetin itself. Our best inhibitors displayed IC₅₀ values in the range of 41–180 nM, which will be a promising contribution for treatment of both canine and human breast cancer.