Dispiro-1,2,4,5-tetraoxanes

A New Class of Antimalarial Peroxides

Jonathan L Vennerstrom, Hong Ling Fu, William Y. Ellis, Steven L. Andersen, Lucia Gerena, Arba L. Ager, James K. Wood

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

Dispiro-1,2,4,5-tetraoxanes 2-4 were synthesized as potential peroxide antimalarial drugs. They had curative activity against Plasmodium berghei in vivo at single doses of 320 and 640 mg/kg which confirms earlier unpublished data. Moreover, artemisinin (1) and 4 had equivalent ED50′s against P. berghei in vivo in the multiple-dose Thompson test; neither showed any evidence of acute toxicity at total doses of more than 12 g/kg. Dispiro-1,2,4,5-tetraoxane 4 had IC50′s comparable to those of 1 against Plasmodium falciparum clones in vitro. These results confirm the potential of dispiro-1,2,4,5-tetraoxanes as a new class of inexpensive peroxide antimalarial drugs.

Original languageEnglish (US)
Pages (from-to)3023-3027
Number of pages5
JournalJournal of Medicinal Chemistry
Volume35
Issue number16
DOIs
StatePublished - Aug 1 1992

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Tetraoxanes
Peroxides
Antimalarials
Plasmodium berghei
Plasmodium falciparum
Clone Cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Vennerstrom, J. L., Fu, H. L., Ellis, W. Y., Andersen, S. L., Gerena, L., Ager, A. L., & Wood, J. K. (1992). Dispiro-1,2,4,5-tetraoxanes: A New Class of Antimalarial Peroxides. Journal of Medicinal Chemistry, 35(16), 3023-3027. https://doi.org/10.1021/jm00094a015

Dispiro-1,2,4,5-tetraoxanes : A New Class of Antimalarial Peroxides. / Vennerstrom, Jonathan L; Fu, Hong Ling; Ellis, William Y.; Andersen, Steven L.; Gerena, Lucia; Ager, Arba L.; Wood, James K.

In: Journal of Medicinal Chemistry, Vol. 35, No. 16, 01.08.1992, p. 3023-3027.

Research output: Contribution to journalArticle

Vennerstrom, JL, Fu, HL, Ellis, WY, Andersen, SL, Gerena, L, Ager, AL & Wood, JK 1992, 'Dispiro-1,2,4,5-tetraoxanes: A New Class of Antimalarial Peroxides', Journal of Medicinal Chemistry, vol. 35, no. 16, pp. 3023-3027. https://doi.org/10.1021/jm00094a015
Vennerstrom, Jonathan L ; Fu, Hong Ling ; Ellis, William Y. ; Andersen, Steven L. ; Gerena, Lucia ; Ager, Arba L. ; Wood, James K. / Dispiro-1,2,4,5-tetraoxanes : A New Class of Antimalarial Peroxides. In: Journal of Medicinal Chemistry. 1992 ; Vol. 35, No. 16. pp. 3023-3027.
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