Evidence for a Common Non‐Heme Chelatable‐Iron‐Dependent Activation Mechanism for Semisynthetic and Synthetic Endoperoxide Antimalarial Drugs

Abstract

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. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z604697_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.