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Synthesis, cytotoxicity and DNA-binding levels of new type binuclear platinum(II) complexes.

Abstract：

:Six new type binuclear platinum(II) complexes (a-f) have been synthesized and characterized by elemental analysis, conductivity, thermal analysis, IR, UV, (1)H NMR and mass spectra techniques. The cytotoxicity of the complexes was tested by MTT and SRB assays. The cell cycle analysis and the levels of total platinum bound to DNA were measured by flow cytometry and ICP-MS, respectively. The results indicate that the complex (a) has no cytotoxicity against HL-60, BGC-823, Bel-7402, KB and Hela, the complexes (b, c, e and f) have weaker cytotoxicity against some tested carcinoma cell lines, the complex (d) has better cytotoxicity against HL-60, BGC-823, Bel-7402, KB, MCF-7, HCT-8 and Hela with respect to the IC(50) values obtained. The cytotoxicity of the complex (d) is equal to that of cisplatin against HL-60 and Bel-7402 (P>0.05), but it has better cytotoxicity than that of cisplatin against BGC-823 and MCF-7 (P<0.05). The complex (d) causes significant G(2)/M arrest and a concomitant decrease of cell population in G(1) and S phases, and the total DNA platination levels of the complex (d) are higher than those of cisplatin under the same experimental conditions. It suggests that the bridging linker has important effect on their cytotoxicity. Indeed, when the bridging linker is dicarboxylic acid, their cytotoxicity is better than that of platinum complexes with an amino acid as bridging linker. The new type binuclear platinum(II) complexes represent a novel class of anticancer agents, which deserves further attention in search of anticancer lead compounds.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Zhang J,Li Y,Sun J,Li W,Gong Y,Zheng X,Cui J,Wang R,Wu J

doi

10.1016/j.ejmech.2009.06.017

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

4772-7

issue

11

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(09)00341-9

journal_volume

44

pub_type

杂志文章

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