Structure–Activity Relationships of Lactone Ring-Opened Analogs of the Antimalarial 1,2,4-Trioxane Artemisinin

Gary H. Posner, David J. McGarvey, Chang Ho Oh, Nirbhay Kumar, Steven R. Meshnick, Wanida Asawamahasadka

Research output: Contribution to journalArticle

Abstract

1,2,4-Trioxane benzylic ethers 8a–e were prepared as simplified, tricyclic versions of the clinically used tetracyclic antimalarial drug artemisinin (1). Five additional artemisinin analogs (9–11) were prepared. Neither water solubility (analogs 8e and 11b) nor chelating ability (analogs 9 and 10), however, produced trioxanes of especially high in vitro antimalarial activity. Trioxane fluorobenzyl ether 8b is the most active in this series (more active than artemisinin) against Plasmodium falciparum parasites in vitro, with substantial activity also in mice infected with Plasmodium berghei parasites and with 10 times higher activity than artemisinin (1) in killing immature P. falciparum gametocytes.

Original languageEnglish (US)
Pages (from-to)607-612
Number of pages6
JournalJournal of medicinal chemistry
Volume38
Issue number4
DOIs
StatePublished - Feb 1 1995

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Posner, G. H., McGarvey, D. J., Oh, C. H., Kumar, N., Meshnick, S. R., & Asawamahasadka, W. (1995). Structure–Activity Relationships of Lactone Ring-Opened Analogs of the Antimalarial 1,2,4-Trioxane Artemisinin. Journal of medicinal chemistry, 38(4), 607-612. https://doi.org/10.1021/jm00004a006