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New, antimalarial, tricyclic 1,2,4-trioxanes: evaluations in mice and monkeys
G H Posner1, C H Oh, H K Webster
1Department of Chemistry, Johns Hopkins University, Baltimore, Maryland.
The American Journal of Tropical Medicine and Hygiene
|April 1, 1994
Summary
Two novel synthetic trioxanes, compounds 8 and 9, demonstrate potent antimalarial activity. They proved as effective as arteether against multidrug-resistant Plasmodium falciparum in preclinical primate studies.
Area of Science:
- Medicinal Chemistry
- Parasitology
- Pharmacology
Background:
- Malaria remains a significant global health challenge, driven by drug-resistant Plasmodium falciparum strains.
- Artemisinin-based therapies are crucial, but resistance necessitates the development of new antimalarial drugs.
Purpose of the Study:
- To evaluate the preclinical antimalarial efficacy of synthetic trioxanes.
- To compare the effectiveness of novel trioxanes against multidrug-resistant Plasmodium falciparum in a primate model.
Main Methods:
- Initial screening of synthetic trioxanes (compounds 3-9) against Plasmodium berghei in mice.
- Selection of promising trioxanes (8 and 9) for further testing in Aotus monkeys infected with multidrug-resistant Plasmodium falciparum.
- Administration of trioxanes 8 and 9, and arteether, via intramuscular injection and monitoring of parasitemia.
Main Results:
- Synthetic trioxanes 8 and 9 showed significant antimalarial activity in Aotus monkeys.
- Trioxane 8 at 48 mg/kg and trioxane 9 at 48 mg/kg achieved curative outcomes in monkeys infected with multidrug-resistant Plasmodium falciparum.
- Both synthetic trioxanes demonstrated comparable efficacy to arteether against the drug-resistant parasite strain.
Conclusions:
- Synthetic trioxanes 8 and 9 are promising candidates for further development as antimalarial drugs.
- These compounds show potential for treating malaria caused by multidrug-resistant Plasmodium falciparum strains.
- Further investigation into these synthetic trioxanes could lead to new therapeutic options for malaria.