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 IC(50) 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.
He
Zhicong
Z
School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Bu
Xianyong
X
Eleftheriou
Alexandra
A
Zihlif
Malik
M
Qing
Zhang
Z
Stewart
Bernard W
BW
Wakelin
Laurence P G
LP
D000609:Aminoacridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics*; D019281:Dimerization; D006801:Humans; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000609:Aminoacridines; D010880:Piperidines; C054505:9-aminoacridine-4-carboxamide; C032727:piperidine; D004247:DNA