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

Abstract

Three platinum complexes in which substituted (7-OMe, 9-NH 2; 7-F, 9-NH 2; and 7-H, 9-NH(CH 2) 2OH) 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) 2OH 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) 2OH 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.