Synthesis and antiproliferative activity of 8-hydroxyquinoline derivatives containing a 1,2,3-triazole moiety

Twelve novel 8-hydroxyquinoline derivatives were synthesized with good yields by performing copper-catalyzed Huisgen 1,3-dipolar cycloaddition ("click" reaction) between an 8-O-alkylated-quinoline containing a terminal alkyne and various aromatic or protected sugar azides. These compounds were evaluated in vitro for their antiproliferative activity on various cancer cell types. Protected sugar derivative 16 was the most active compound in the series, exhibiting potent antiproliferative activity and high selectivity toward ovarian cancer cells (OVCAR-03, GI(50) < 0.25 mu g mL(-1)); this derivative was more active than the reference drug doxorubicin (OVCAR-03, GI(50) = 0.43 mu g mL(-1)). In structure-activity relationship (SAR) studies, the physico-chemical parameters of the compounds were evaluated and docking calculations were performed for the alpha-glucosidase active site to predict the possible mechanism of action of this series of compounds. (C) 2014 Elsevier Masson SAS. All rights reserved.