New, antimalarial, tricyclic 1,2,4-trioxanes: Evaluations in mice and monkeys

G. H. Posner, C. H. Oh, H. K. Webster, A. L. Ager, R. N. Rossan

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

We have concluded initial preclinical studies with synthetic trioxanes numbered 3-9 and have compared them with artemisinin (numbered 1) using CD 1 mice infected with Plasmodium berghei. Based on their antimalarial effectiveness in mice, two of these synthetic trioxanes were selected for evaluation in Aotus monkeys infected with multidrug-resistant (MDR) P. falciparum. Trioxane numbered 8 (12 and 48 mg/kg), trioxane numbered 9 (12 and 48 mg/kg) and arteether (numbered 2, 48 mg/kg) were administered intramuscularly in three 12-hr doses to A. lemurinus lemurinus (Panamanian owl monkeys) infected with the Vietnam Smith/RE strain of P. falciparum and monitored for parasitemia. Trioxane numbered 8 at 12 mg/kg cleared parasitemia in two monkeys, but recrudescence occurred in one animal. Treatment of the recrudescent infection with 48 mg/kg was curative. Infections in two monkeys treated initially with 48 mg/kg were cured (six- month follow-up). Trioxane numbered 9 produced a similar outcome: 12 mg/kg suppressed parasitemia in two monkeys but was not curative: however, 48 mg/kg cured infections in all four monkeys treated. These preliminary observations show synthetic trioxanes numbered 8 and 9 to be as effective as arteether (numbered 2) against MDR in P. falciparum in the Aotus monkey.

Original languageEnglish (US)
Pages (from-to)522-526
Number of pages5
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume50
Issue number4
DOIs
StatePublished - Jan 1 1994

ASJC Scopus subject areas

  • Parasitology
  • Virology
  • Infectious Diseases

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