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

Using assays based on the inhibition of restriction enzyme cleavage of plas mid and synthetic DNA, the complex (2-amino-2-methyl-3-butanone oxime)dichl oroplatinum(II), [PtCl2(ambo)], has been shown to have an increased tendenc y for binding to adenine-rich sequences when compared to cis-[PtCl2(NH3)(2) ] (cisplatin). [PtCl2(ambo)] was found to form substantially fewer interstr and adducts than does cisplatin. The in vitro cytotoxicity of [PtCl2(ambo)] against a human bladder cancer cell line was determined and found to be mo re than two orders of magnitude lower than that of cisplatin, yet it was al so found to be equally effective at passing into cells and binding to isola ted DNA.