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

Xiaofang Wang, Darren J. Creek, Charles E. Schiaffo, Yuxiang Dong, Jacques Chollet, Christian Scheurer, Sergio Wittlin, Susan A. Charman, Patrick H Dussault, James K. Wood, Jonathan L Vennerstrom

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4542-4545
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number16
DOIs
StatePublished - Aug 15 2009

Fingerprint

Peroxides
Alkylation
Antimalarials
Heme
Iron
Reaction rates
1,2,4-trioxane

Keywords

  • 1,2,4-Trioxane
  • 1,2,4-Trioxepane
  • 1,2,4-Trioxolane
  • Antimalarial
  • Artemisinin
  • Peroxide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

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. / Wang, Xiaofang; Creek, Darren J.; Schiaffo, Charles E.; Dong, Yuxiang; Chollet, Jacques; Scheurer, Christian; Wittlin, Sergio; Charman, Susan A.; Dussault, Patrick H; Wood, James K.; Vennerstrom, Jonathan L.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 19, No. 16, 15.08.2009, p. 4542-4545.

Research output: Contribution to journalArticle

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AU - Dong, Yuxiang

AU - Chollet, Jacques

AU - Scheurer, Christian

AU - Wittlin, Sergio

AU - Charman, Susan A.

AU - Dussault, Patrick H

AU - Wood, James K.

AU - Vennerstrom, Jonathan L

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