Evidence for a common non-heme chelatable-iron-dependent activation mechanism for semisynthetic and synthetic endoperoxide antimalarial drugs

Paul A. Stocks, Patrick G. Bray, Victoria E. Barton, Mohammed Al-Helal, Michael Jones, Nuna C. Araujo, Peter Gibbons, Stephen A. Ward, Ruth H. Hughes, Giancarlo A. Biagini, Jill Davies, Richard Amewu, Amy E. Mercer, Gemma Ellis, Paul M. O'Neill

Research output: Contribution to journalArticlepeer-review

120 Citations (Scopus)

Abstract

(Chemical Equation Presented) The iron-y of fate: Isobole analyses of fluorescently labeled antimalarial endoperoxides with chelators selective for non-heme iron, and laser confocal microscopy studies within living malaria parasites have shown that the semisynthetic analogues of artemisinin and synthetic endoperoxides (see example) share a common mechanism of action involving chelatable-iron-mediated bioactivation (see images) and irreversible alkylation of parasite targets.

Original languageEnglish
Pages (from-to)6278-6283
Number of pages6
JournalAngewandte Chemie - International Edition
Volume46
Issue number33
DOIs
Publication statusPublished - 2007
Externally publishedYes

Keywords

  • Antimalarial agents
  • Chelates
  • Confocal imaging
  • Fluorescence
  • Iron

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