Synthesis and biological evaluation of novel chloroethylaminoanthraquinones with potent cytotoxic activity against cisplatin-resistant tumor cells

  • J Med Chem. 2004 Mar 25;47(7):1856-9. doi: 10.1021/jm031070u.
Klaus Pors  1 ,  Zennia Paniwnyk ,  Ketan C Ruparelia ,  Paul H Teesdale-Spittle ,  John A Hartley ,  Lloyd R Kelland ,  Laurence H Patterson
Affiliations
  • 1. Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, 29-39 Brunswick Square, University of London, London WC1N 1AX, UK.
PMID: 15027879 DOI: 10.1021/jm031070u
Abstract

Novel 1- and 1,4-substituted chloroethylaminoanthraquinones with DNA binding and alkylating properties along with their respective hydroxyethylaminoanthraquinone intermediates were synthesized. Selected chloroethylaminoanthraquinones were shown to cross-link DNA and alkylate guanines (at low nM concentration) with a preference for reaction sites containing 5'-PyG. A compound (Alchemix) with the bis-chloroethyl functionality confined to one side chain alkylated but did not cross-link DNA. All the 1,4-disubstituted chloroethylaminoanthraquinones were potently cytotoxic (nM IC(50)s) against cisplatin-resistant ovarian Cancer cell lines.