DNA threading bis(9-aminoacridine-4-carboxamides): Effects of piperidine sidechains on DNA binding, cytotoxicity and cell cycle arrest

We describe the synthesis of a series of DNA-threading bis(9-aminoacridine-4-carboxamides) comprising ethylpiperidino and N-methylpiperidin-4-yl sidechains, joined via neutral flexible alkyl chains, charged flexible polyamine chains and a semi-rigid charged piperazine linker. Their cytotoxicity towards human leukaemic cells gives IC50 values ranging from 99 to 1100 nM, with the ethylpiperidino series generally being more cytotoxic than the N-methylpiperidin-4-yl series. Measurements with supercoiled DNA indicate that they bisintercalate.

A series of bis(9-aminoacridine-4-carboxamides) with ethylpiperidino and N-methylpiperidin-4-yl sidechains were synthesized and evaluated for the effects on DNA binding, cytotoxicity and cell cycle arrest.Figure optionsDownload as PowerPoint slide