Substituted 9-aminoacridine-4-carboxamide (cas 106988-43-6)s tethered to platinum(II)diamine complexes: Chemistry, cytotoxicity and DNA sequence selectivity

Add time:08/10/2019    Source:sciencedirect.com

Three platinum complexes in which substituted (7-OMe, 9-NH2; 7-F, 9-NH2; and 7-H, 9-NH(CH2)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 IC50 values in HeLa cells, when compared with the parent 7-H, 9-NH2 compound. The 7-F and 9-NH(CH2)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(CH2)2OH and especially the 7-OMe substituents, resulted in reduced DNA binding. This correlated well with the IC50 cytotoxicity values. However, the DNA sequence selectivity was unaffected by the addition of these moieties.

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