Increased targeting of adenine-rich sequences by (2-amino-2-methyl 3-butanone oxime)dichloroplatinum(II) and investigations into its low cytotoxicity

被引:21
作者
Hambley, TW [1 ]
Ling, ECH
O'Mara, S
McKeage, MJ
Russell, PJ
机构
[1] Univ Sydney, Sch Chem, Sydney, NSW 2006, Australia
[2] Prince Wales Hosp, Oncol Res Ctr, Randwick, NSW 2031, Australia
来源
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY | 2000年 / 5卷 / 06期
基金
澳大利亚研究理事会;
关键词
platinum anti-cancer drugs; DNA binding; sequence selectivity; drug design; cellular uptake;
D O I
10.1007/s007750000151
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Using assays based on the inhibition of restriction enzyme cleavage of plasmid and synthetic DNA, the complex (2-amino-2-methyl-3-butanone oxime)dichloroplatinum(II), [PtCl2(ambo)], has been shown to have an increased tendency for binding to adenine-rich sequences when compared to cis-[PtCl2(NH3)(2)] (cisplatin). [PtCl2(ambo)] was found to form substantially fewer interstrand adducts than does cisplatin. The in vitro cytotoxicity of [PtCl2(ambo)] against a human bladder cancer cell line was determined and found to be more than two orders of magnitude lower than that of cisplatin, yet it was also found to be equally effective at passing into cells and binding to isolated DNA.
引用
收藏
页码:675 / 681
页数:7
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