Spiroadamantyl 1,2,4-Trioxolane, 1,2,4-Trioxane, and 1,2,4-Trioxepane Pairs: Relationship Between Peroxide Bond Iron(II) Reactivity, Heme Alkylation Efficiency, and Antimalarial Activity

Authors

Xiaofang Wang, The University of Nebraska Medical CenterFollow
Darren J. Creek, Monash University, Parkville, Victoria, Australia
Yuxiang Dong, The University of Nebraska Medical CenterFollow
Jacques Chollet, Swiss Tropical Institute, Basel
Christian Scheurer, Swiss Tropical Institute, Basel
Sergio Wittlin, Swiss Tropical Institute, Basel
Susan A. Charman, Monash University, Parkville, Victoria, Australia
Patrick H. Dussault, The University of Nebraska, LincolnFollow
James K. Wood, The University of Nebraska at OmahaFollow
Jonathan L. Vennerstrom, The University of Nebraska Medical CenterFollow

Document Type

Article

Publication Date

8-1-2009

Publication Title

Bioorganic & Medicinal Chemistry Letters

Volume

19

Issue

16

First Page

4542

Last Page

4545

Abstract

These data suggest that iron(II) reactivity for a set of homologous spiroadamantyl 1,2,4-trioxolane, 1,2,4-trioxane, and 1,2,4-trioxepane peroxide heterocycles is a necessary, but insufficient, property of animalarial peroxides. Heme alkylation efficiency appears to give a more accurate prediction of antimalarial activity than FeSO4-mediated reaction rates, suggesting that antimalarial activity is not merely dependent on peroxide bond cleavage, but also on the ability of reactive intermediates to alkylate heme or other proximal targets.

Comments

Copyright © 2009, American Chemical Society.

Recommended Citation

Wang, Xiaofang; Creek, Darren J.; Dong, Yuxiang; Chollet, Jacques; Scheurer, Christian; Wittlin, Sergio; Charman, Susan A.; Dussault, Patrick H.; Wood, James K.; and Vennerstrom, Jonathan L., "Spiroadamantyl 1,2,4-Trioxolane, 1,2,4-Trioxane, and 1,2,4-Trioxepane Pairs: Relationship Between Peroxide Bond Iron(II) Reactivity, Heme Alkylation Efficiency, and Antimalarial Activity" (2009). Chemistry Faculty Publications. 3.
https://digitalcommons.unomaha.edu/chemfacpub/3