Dispiro-1,2,4,5-tetraoxanes: A new class of antimalarial peroxides

Jonathan L. Vennerstrom, Hong Ning Fu, William Y. Ellis, Arba L. Ager, James K. Wood, Arba L Ager, Lucia Gerena, Wilbur K. Milhous

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

Dispiro-1,2,4,5-tetraoxanee 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had curative activity against Plasmodium berghei in vivo at single doses of 320 and 640 mg/kg which confirms earlier unpublished data.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
StatePublished - 1992

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Tetraoxanes
Plasmodium berghei
Peroxides
Antimalarials
Plasmodium falciparum
Inhibitory Concentration 50
Toxicity
Clone Cells

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Vennerstrom, J. L., Fu, H. N., Ellis, W. Y., Ager, A. L., Wood, J. K., Ager, A. L., ... Milhous, W. K. (1992). Dispiro-1,2,4,5-tetraoxanes: A new class of antimalarial peroxides. Journal of Medicinal Chemistry, 35(16), 3023-3027.

Dispiro-1,2,4,5-tetraoxanes : A new class of antimalarial peroxides. / Vennerstrom, Jonathan L.; Fu, Hong Ning; Ellis, William Y.; Ager, Arba L.; Wood, James K.; Ager, Arba L; Gerena, Lucia; Milhous, Wilbur K.

In: Journal of Medicinal Chemistry, Vol. 35, No. 16, 1992, p. 3023-3027.

Research output: Contribution to journalArticle

Vennerstrom, JL, Fu, HN, Ellis, WY, Ager, AL, Wood, JK, Ager, AL, Gerena, L & Milhous, WK 1992, 'Dispiro-1,2,4,5-tetraoxanes: A new class of antimalarial peroxides', Journal of Medicinal Chemistry, vol. 35, no. 16, pp. 3023-3027.
Vennerstrom JL, Fu HN, Ellis WY, Ager AL, Wood JK, Ager AL et al. Dispiro-1,2,4,5-tetraoxanes: A new class of antimalarial peroxides. Journal of Medicinal Chemistry. 1992;35(16):3023-3027.
Vennerstrom, Jonathan L. ; Fu, Hong Ning ; Ellis, William Y. ; Ager, Arba L. ; Wood, James K. ; Ager, Arba L ; Gerena, Lucia ; Milhous, Wilbur 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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