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

• Published in: Journal of biological inorganic chemistry Vol. 5; no. 6; pp. 675 - 681
• Main Authors: Hambley, T W, Ling, E C, O'Mara, S, McKeage, M J, Russell, P J
• Format: Journal Article
• Language: English
• Published: Germany 01-12-2000
• Subjects: Adenine - metabolism; Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Base Sequence; Cattle; DNA - chemistry; DNA - drug effects; DNA - metabolism; Drug Design; Drug Screening Assays, Antitumor; Humans; Molecular Sequence Data; Organoplatinum Compounds - chemistry; Organoplatinum Compounds - metabolism; Organoplatinum Compounds - pharmacology; Tumor Cells, Cultured
• ISSN: 0949-8257; 1432-1327
• DOI: 10.1007/s007750000151

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.