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Dinuclear Platinum(II) Complexes with Bone‐Targeting Groups as Potential Anti‐Osteosarcoma Agents
Author(s) -
Zhang Zhenqin,
Wang Xiaoyong,
Luo Cheng,
Zhu Chengcheng,
Wang Kun,
Zhang Changli,
Guo Zijian
Publication year - 2017
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201700577
Subject(s) - chemistry , osteosarcoma , platinum , stereochemistry , methylene , cytotoxicity , phosphonate , apoptosis , in vitro , medicinal chemistry , cancer research , biochemistry , medicine , catalysis
Abstract Osteosarcoma is the most common malignant bone tumor primarily affecting 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(NH 3 ) 2 Cl] 2 (PD)} (NO 3 ) 2 ( 1 ), {[ cis ‐Pt(NH 3 ) 2 Cl] 2 (PDBP)} (NO 3 ) 2 ( 2 ), {[ cis ‐Pt(DACH)Cl] 2 (PD)} (NO 3 ) 2 ( 3 ), and {[ cis ‐Pt(DACH)Cl] 2 (PDBP)} (NO 3 ) 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 1 H, 13 C, 195 Pt or 31 P NMR spectroscopy and HR‐MS. ICP‐MS studies showed that considerable amounts of Pt accumulate 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 arrests the cell cycle mainly in the G2 or M phase. The results demonstrate that dinuclear platinum(II) complexes with bone‐targeting groups could be anticancer agents for osteosarcoma.