title: Original multivalent copper(II)-conjugated phosphorus dendrimers and corresponding mononuclear copper(II) complexes with antitumoral activities.
abstract: 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.
authors: Institute of Nanomaterials & Nanotechnology, Moroccan Advanced Science, Innovation and Research Foundation, Avenue de l'Armée Royale, Madinat El Irfane, 10100, Rabat, Morocco.
authors: Nabil
authors: N
authors: El Brahmi
authors: Saïd
authors: S
authors: El Kazzouli
authors: Serge M
authors: SM
authors: Mignani
authors: El Mokhtar
authors: el M
authors: Essassi
authors: Geneviève
authors: G
authors: Aubert
authors: Régis
authors: R
authors: Laurent
authors: Anne-Marie
authors: AM
authors: Caminade
authors: Mosto M
authors: MM
authors: Bousmina
authors: Thierry
authors: T
authors: Cresteil
authors: Jean-Pierre
authors: JP
authors: Majoral
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000737:chemistry; D002347:Carps; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003300:Copper / Q000737:chemistry*; D050091:Dendrimers / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D050997:Nanomedicine; D010758:Phosphorus / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D050091:Dendrimers; D010758:Phosphorus; D003300:Copper