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

Zhicong He; Xianyong Bu; Alexandra Eleftheriou; Malik Zihlif; Zhang Qing; Bernard W Stewart; Laurence P G Wakelin

doi:10.1016/j.bmc.2008.02.063

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

Bioorg Med Chem. 2008 Apr 15;16(8):4390-400. doi: 10.1016/j.bmc.2008.02.063. Epub 2008 Feb 23.

Authors

Zhicong He¹, Xianyong Bu, Alexandra Eleftheriou, Malik Zihlif, Zhang Qing, Bernard W Stewart, Laurence P G Wakelin

Affiliation

¹ School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.

PMID: 18329887
DOI: 10.1016/j.bmc.2008.02.063

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminoacridines / chemical synthesis*
Aminoacridines / chemistry
Aminoacridines / toxicity*
Cell Cycle / drug effects*
Cell Line, Tumor
DNA / genetics*
Dimerization
Humans
Molecular Structure
Piperidines / chemistry*
Structure-Activity Relationship

Substances

Aminoacridines
Piperidines
9-aminoacridine-4-carboxamide
piperidine
DNA