Novel multivalent copper(II)-conjugated phosphorus dendrimers and their corresponding mononuclear copper(II) complexes were synthesized, characterized, and screened for antiproliferative activity against human cancer cell lines. Selected copper ligands were grafted on the surface of phosphorus dendrimers of generation G(n) (n = 1 to 3): N-(pyridin-2-ylmethylene)ethanamine for dendrimers 1G(n), N-(di(pyridin-2-yl)methylene)ethanamine for dendrimers 2G(n), and 2-(2-methylenehydrazinyl)pyridine for dendrimers 3G(n). The results indicated that the most potent derivatives are 1G(n) and 1G(n)-Cu versus 2G(n), 2G(n)-Cu, and 3G(n), 3G(n)-Cu. A direct relationship between the growth inhibitory effect and the number of terminal moieties or the amount of copper complexed to the dendrimer was observed in copper-complexed 1 series and noncomplexed 1 series. These data clearly suggested that cytotoxicity increased with the number of terminal moieties available and was boosted by the presence of complexed Cu atoms. Importantly, no cytotoxic effect was observed with CuCl2 at the same concentrations. Finally, 1G3 and 1G3-Cu have been selected for antiproliferative studies against a panel of tumor cell lines: 1G3 and 1G3-Cu demonstrated potent antiproliferative activities with IC50 values ranging 0.3-1.6 μM. Interestingly, the complexation of the terminal ligands of 1G3 dendrimers by copper(II) metal strongly increased the IC50 values in noncancer cells lines referred to as "safety" cell lines.
These data can be used to inform a resistance management strategy that requires comprehensive information concerning malaria vector species composition in the areas of interest, and their susceptibility to the insecticides proposed for their control.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.