A chloroquine-like molecule designed to reverse resistance in Plasmodium falciparum

Steven J. Burgess, Audrey Selzer, Jane Xu Kelly, Martin J. Smilkstein, Michael K. Riscoe, David H. Peyton

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

A class of hybrid molecules which we term 'reversed chloroquines' (RCQs) was designed, and a prototype molecule, N′-(7-chloroquinolin-4-yl)-N-[3- (10,11-dihydrodibenzo[bf]azepin-5-yl)propyl]-N-methylpropane-1,3-diamine (1), was synthesized and tested against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. An in vitro assay against the two strains indicated that 1 was effective at low-nM concentrations against both strains. A preliminary study in mice demonstrated oral efficacy against P. chabaudi and the absence of obvious toxicity. The RCQ approach therefore appears to be feasible.

Original languageEnglish (US)
Pages (from-to)5623-5625
Number of pages3
JournalJournal of Medicinal Chemistry
Volume49
Issue number18
DOIs
StatePublished - Sep 7 2006

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Burgess, S. J., Selzer, A., Kelly, J. X., Smilkstein, M. J., Riscoe, M. K., & Peyton, D. H. (2006). A chloroquine-like molecule designed to reverse resistance in Plasmodium falciparum. Journal of Medicinal Chemistry, 49(18), 5623-5625. https://doi.org/10.1021/jm060399n