Copper(i)-catalysed azide–alkyne cycloaddition and antiproliferative activity of mono- and bis-1,2,3-triazole derivatives

Abstract

A series of mono- and bis-1,2,3-triazole-based molecular architectures were prepared in excellent yields via the standard copper(I)-catalysed azide–alkyne cycloaddition (CuAAC) of substituted aromatic derivatives, comprising one or two terminal alkyne groups with a selection of aromatic azides. In vitro antiproliferative activities of the novel 1,2,3-triazoles were evaluated against four human cancer cell lines, including HepG-2, MCF-7, HCT-116, and A549 via the MTT assay. Among all the tested compounds, bis-1,2,3-triazole derivative 16 exhibited potent activity against HepG-2 compared to the standard reference anticancer drug doxorubicin. The mono-1,2,3-triazole 9, mono-1,2,3-triazole 13, and bis-1,2,3-triazole 17 showed comparable activities relative to doxorubicin in the case of the antiproliferative evaluation against MCF-7. With respect to HCT-116 biological activity screening, all the evaluated compounds except mono-1,2,3-triazole derivatives 10 and 11 showed potent antiproliferative activities relative to doxorubicin. Regarding the lung cancer cell line A549, mono-1,2,3-triazole 9, bis-1,2,3-triazole 15, bis-1,2,3-triazoles 21, and bis-1,2,3-triazoles 22 displayed slightly lower activities relative to doxorubicin, while the rest of the tested compounds exhibited moderate activities. Only compound 18 showed significant toxicity on the human healthy cells relative to both human lung and liver cancer types. The novel mono- and bis-1,2,3-triazoles developed in this work can ideally be utilised as potent candidates for pharmaceutical applications.