A mild and versatile method based on Cu-catalyzed [2+3] cycloaddition (Huisgen-Meldal-
Sharpless reaction) was developed to tether 3,3’-((4-(prop-2-yn-1-yloxy)phenyl)methylene)bis(4-
hydroxyquinolin-2(1H)-ones) with 4-azido-2-quinolones in good yields. This methodology allowed
attaching three quinolone molecules via a triazole linker with the proposed mechanism. The products
are interesting precursors for their anti-proliferative activity. Compound 8g was the most active one,
achieving IC50 = 1.2 0.2 M and 1.4 0.2 M against MCF-7 and Panc-1 cell lines, respectively.
Moreover, cell cycle analysis of cells MCF-7 treated with 8g showed cell cycle arrest at the G2/M
phase (supported by Caspase-3,8,9, Cytochrome C, BAX, and Bcl-2 studies). Additionally, significant
pro-apoptotic activity is indicated by annexin V-FITC staining.