New, antimalarial, tricyclic 1,2,4-trioxanes: evaluations in mice and monkeys
| Autor: | G. H. Posner, R. N. Rossan, A. L. Ager, C. H. Oh, H. K. Webster |
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| Rok vydání: | 1994 |
| Předmět: |
Bridged-Ring Compounds
Trioxane Plasmodium berghei Parasitemia Pharmacology chemistry.chemical_compound Antimalarials Mice Heterocyclic Compounds Virology parasitic diseases medicine Animals Artemisinin Malaria Falciparum Protozoal disease chemistry.chemical_classification biology Molecular Structure biology.organism_classification medicine.disease Artemisinins Malaria Infectious Diseases chemistry Aotus trivirgatus Immunology Parasitology Sesquiterpenes Tricyclic Clearance medicine.drug |
| Zdroj: | The American journal of tropical medicine and hygiene. 50(4) |
| ISSN: | 0002-9637 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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