Title
Dinuclear platinum(II) complexes with bone-targeting groups as potential anti-osteosarcoma agents
Author
Zijian Guo, Zhenqin Zhang, Xiaoyong Wang, Cheng Luo, Chengcheng Zhu, Changli Zhang, Kun Wang
Year
2017
Journal
Chemistry A European Journal
Abstract
Osteosarcoma is the most common malignant bone tumor primarily affects adolescents. Targeted platinum(II) complexes are promising candidates for overcoming the general toxicity of conventional platinum anticancer drugs. In this study four dinuclear platinum(II) complexes, {[cis-Pt(NH3)2Cl]2(PD)} (NO3)2 (1), {[cis-Pt(NH3)2Cl]2(PDBP)} (NO3)2 (2), {[cis-Pt(DACH)Cl]2(PD)} (NO3)2 (3), {[cis-Pt(DACH)Cl]2(PDBP)} (NO3)2 (4) [PD = 5,5′-carbonylbis(2-(2-(pyridin-2-yl)ethyl)isoindoline-1,3-dione), PDBP = tetraethyl (((bis(1,3-dioxo-2-(2-(pyridin-2-yl)ethyl)isoindolin-5-yl)methylene)amino) methylene)bis(phosphonate), DACH = 1,2-diaminocyclohexane)], were designed and synthesized. The complexes were fully characterized by 1H-, 13C-, 195Pt- or 31P-NMR and HR-MS. ICP-MS studies showed that considerable Pt accumulates in U2Os osteosarcoma cells. The interactions of the complexes with calf thymus DNA and plasmid pUC19 DNA were investigated using CD and gel electrophoresis, which indicated that the complexes can react with DNA. The in vitro cytotoxicity showed that 2 is the most potent complex towards U2Os cells. The cellular inhibition mode was examined by flow cytometry. Complex 2 kills U2Os cells predominately through an apoptotic pathway and arrest the cell cycle mainly in G2 or M phase. The results demonstrate that dinuclear platinum(II) complexes with bone-targeting groups could be anticancer agents for osteosarcoma.
Instrument
J-810
Keywords
Circular dichroism, DNA binding, DNA structure, Coordination chemistry, Biochemistry