Self-Assembled Supramolecular Hetero-Bimetallacycles for Anticancer Potency by Intracellular Release

被引:42
作者
Mishra, Anurag [1 ]
Lee, Seung Chang [1 ]
Kaushik, Neha [2 ]
Cook, Timothy R. [3 ]
Choi, Eun Ha [2 ]
Kaushik, Nagendra Kumar [2 ]
Stang, Peter J. [3 ]
Chi, Ki-Whan [1 ]
机构
[1] Univ Ulsan, Dept Chem, Ulsan 680749, South Korea
[2] Kwangwoon Univ, Plasma Biosci Res Ctr, Seoul 139701, South Korea
[3] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA
基金
新加坡国家研究基金会;
关键词
antitumor agents; biological activity; ligands; metallacycles; self-assembly; supramolecular chemistry; DNA-BINDING; MOLECULAR RECOGNITION; INORGANIC-CHEMISTRY; SELECTIVE DETECTION; COORDINATION; RUTHENIUM; COMPLEXES; DESIGN; PLATINUM; SQUARE;
D O I
10.1002/chem.201403372
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Two new tetracationic hetero-bimetallacycles, compounds 4 and 5, have been constructed from an N,N-bis(4-(pyridin-4-ylethynyl)phenyl)pyridine-2,6-dicarboxamide ligand (1), and cis-blocked complexes [M(dppf)(OTf)(2)] (dppf=1,1-bis(diphenylphosphino)ferrocene; OTf=trifluoromethanesulfonate; M=Pd (2), Pt (3)) in CH3NO2/CH2Cl2 (1:1) solvent. Both complexes were isolated with adequate yields as triflate salts and were then characterized using H-1, C-13, and (PNMR)-P-31 spectroscopy, elemental analysis, UV/Vis spectroscopy, and high-resolution electrospray mass spectrometry (HR-ESMS). The molecular structure of 4 was determined by molecular mechanics force-field calculations. The cytotoxic effect of both new complexes were analyzed against T98G (brain tumor), KB (head and neck cancer), SNU-80 (thyroid cancer), and HEK-293 non-malignant cell lines. The cytotoxicity of complexes 4 and 5 were found to be considerably more effective against cancer cells than reference drug cisplatin. Annexin-V/PI staining, caspase-3/7 activity, and the reduction in mitochondrial membrane potential justify a significant level of apoptosis in complex-treated cells.
引用
收藏
页码:14410 / 14420
页数:11
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