Substituted 9-aminoacridine-4-carboxamides tethered to platinum(II)diamine complexes: chemistry, cytotoxicity and DNA sequence selectivity.

Three platinum complexes in which substituted (7-OMe, 9-NH(2); 7-F, 9-NH(2); and 7-H, 9-NH(CH(2))(2)OH) 9-aminoacridine-4-carboxamides were tethered to a platinum(II)diamine moiety were synthesised and characterised at the chemical and biological level. These variants showed a decrease in cytotoxicity, as measured by IC(50) values in HeLa cells, when compared with the parent 7-H, 9-NH(2) compound. The 7-F and 9-NH(CH(2))(2)OH substituents gave rise to a small decrease in cytotoxicity, and the 7-OMe substituent resulted in a larger decrease in cytotoxicity. Their binding to purified pUC19 plasmid DNA was investigated and it was found that the addition of 7-F, 9-NH(CH(2))(2)OH and especially the 7-OMe substituents, resulted in reduced DNA binding. This correlated well with the IC(50) cytotoxicity values. However, the DNA sequence selectivity was unaffected by the addition of these moieties. (c) 2010 Elsevier Inc. All rights reserved.