Increased targeting of adenine-rich sequences by (2-amino-2-methyl-3-butanone oxime)dichloroplatinum(II) and investigations into its low cytotoxicity |
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Authors: | Trevor W. Hambley Edwina C.H. Ling Shaun O'Mara Mark J. McKeage Pamela J. Russell |
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Affiliation: | School of Chemistry, University of Sydney, NSW, Australia. t.hambley@chem.usyd.edu.au |
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Abstract: | 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. |
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