Dispiro-1,2,4,5-tetraoxanes: a new class of antimalarial peroxides
| Autor: | Arba L. Ager, James K. Wood, Hong Ning Fu, Jonathan L. Vennerstrom, William Y. Ellis, Wilbur K. Milhous, Lucia Gerena, Steven L. Andersen |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Ethylene Oxide
Male Plasmodium berghei Stereochemistry Plasmodium falciparum Pharmacology Peroxide Antimalarials Mice chemistry.chemical_compound In vivo parasitic diseases Drug Discovery medicine Animals Spiro Compounds Tetraoxanes Artemisinin IC50 Molecular Structure biology Chemistry biology.organism_classification Acute toxicity Peroxides Molecular Medicine medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 35:3023-3027 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00094a015 |
| Popis: | 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had curative activity against Plasmodium berghei in vivo at single doses of 320 and 640 mg/kg which confirms earlier unpublished data.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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|