Comparative antimalarial activities of six pairs of 1,2,4,5-tetraoxanes (peroxide dimers) and 1,2,4,5,7,8-hexaoxonanes (peroxide trimers)

Yuxiang Dong; Darren Creek; Jacques Chollet; Hugues Matile; Susan A Charman; Sergio Wittlin; James K Wood; Jonathan L Vennerstrom

doi:10.1128/AAC.00264-07

Comparative antimalarial activities of six pairs of 1,2,4,5-tetraoxanes (peroxide dimers) and 1,2,4,5,7,8-hexaoxonanes (peroxide trimers)

Antimicrob Agents Chemother. 2007 Aug;51(8):3033-5. doi: 10.1128/AAC.00264-07. Epub 2007 May 7.

Authors

Yuxiang Dong¹, Darren Creek, Jacques Chollet, Hugues Matile, Susan A Charman, Sergio Wittlin, James K Wood, Jonathan L Vennerstrom

Affiliation

¹ College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198-6025, USA.

Abstract

Six tetraoxanes had 50% inhibitory concentrations in the range of 10 to 100 ng/ml against Plasmodium falciparum, whereas the corresponding hexaoxonanes had minimal antimalarial activity. The lack of iron-mediated reactivity of the hexaoxonanes may explain their low activity compared to the tetraoxanes, the latter of which are able to undergo iron(II)-mediated activation.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antimalarials / chemistry
Antimalarials / pharmacology*
Dimerization
Drug Resistance
Inhibitory Concentration 50
Iron / metabolism
Mice
Models, Molecular
Parasitic Sensitivity Tests
Peroxides / chemistry
Peroxides / pharmacology*
Plasmodium berghei / drug effects*
Plasmodium falciparum / drug effects*
Structure-Activity Relationship
Tetraoxanes / chemistry
Tetraoxanes / pharmacology*

Substances

Antimalarials
Peroxides
Tetraoxanes
Iron