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- Title
Synthesis, Structure, and Antimalarial Activity of Tricyclic 1,2,4-Trioxanes Related to Artemisinin.
- Authors
Jefford, Charles W.; Velarde, Javier A.; Bernardinelli, Gérald; Bray, Dorothy H.; Warhurst, David C.; Milhous, Wilbur K.
- Abstract
Two sets of tricyclic 1,2,4-trioxanes containing the ABC ( 10, 11) and ACD ring portions ( 21, 22, 32, 33, 37, and 38) of artemisinin ( 1) were synthesized by successive photo-oxygenation of appropriate enol-ether precursors to 1,2-dioxanes and inter- and intramolecular reaction with a carbonyl compound or oxo-substituted side-chain. The structures of 10, 21, and 22 were determined by X-ray analysis. The anti-malarial activity of all trioxanes, except 37 and 38, was evaluated in vitro against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum parasites. Trioxanes 11 and 21 were as active as artemisinin ( 1). It was found that neither the lactone function nor rings B and D of 1 were essential for activity. A possible pharmacophore for artemisinin-like activity, which embodies a spirocyclopentane group attached to C(3) of 1,2,4-trioxane, was proposed.
- Publication
Helvetica Chimica Acta, 1993, Vol 76, Issue 8, p2775
- ISSN
0018-019X
- Publication type
Article
- DOI
10.1002/hlca.19930760804