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Peroxide Bond-Dependent Antiplasmodial Specificity of Artemisinin and OZ277 (RBx11160)

Swiss Tropical Institute, Socinstrasse 57, CH-4002 Basel, Switzerland,¹ College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198-6025,² F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland,³ Institute of Parasitology, University of Bern, CH-3012 Bern, Switzerland⁴

Received 14 February 2007/ Returned for modification 30 April 2007/ Accepted 1 June 2007

Using nonperoxidic analogs of artemisinin and OZ277 (RBx11160), the strong in vitro antiplasmodial activities of the latter two compounds were shown to be peroxide bond dependent. In contrast, the weak activities of artemisinin and OZ277 against six other protozoan parasites were peroxide bond independent. These data support the iron-dependent artemisinin alkylation hypothesis.

Published ahead of print on 11 June 2007.