New type of febrifugine analogues, bearing a quinolizidine moiety, show potent antimalarial activity against Plasmodium malaria parasite

Yoshiaki Takaya, Hidehisa Tasaka, Tomoyuki Chiba, Koji Uwai, Masa Aki Tanitsu, Hye Sook Kim, Yusuke Wataya, Masatomo Miura, Mitsuhiro Takeshita, Yoshiteru Oshima

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Febrifugine (1) and isofebrifugine (2), isolated from the roots of Dichroa febrifuga Lour. (Chinese name: Chang Shah), are active principles against malaria. Adducts of 1 and 2 with acetone, Df-1 (3) and Df-2 (4), respectively, were obtained using silica gel and acetone. They showed high activity against P. falciparum malaria in vitro. Compound 3 was found to be equally effective against P. berghei in vivo as the clinically used drug chloroquine, whereas 4 showed only 1/24 of the activity of 3. Metabolism studies of these compounds revealed that compound 4 is readily metabolized in mouse liver. Accordingly, the dose of 4 must be higher than that of 3 to attain blood levels sufficient for a favorable therapeutic effect.

Original languageEnglish
Pages (from-to)3163-3166
Number of pages4
JournalJournal of medicinal chemistry
Volume42
Issue number16
DOIs
Publication statusPublished - Aug 12 1999

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of 'New type of febrifugine analogues, bearing a quinolizidine moiety, show potent antimalarial activity against Plasmodium malaria parasite'. Together they form a unique fingerprint.

  • Cite this

    Takaya, Y., Tasaka, H., Chiba, T., Uwai, K., Tanitsu, M. A., Kim, H. S., Wataya, Y., Miura, M., Takeshita, M., & Oshima, Y. (1999). New type of febrifugine analogues, bearing a quinolizidine moiety, show potent antimalarial activity against Plasmodium malaria parasite. Journal of medicinal chemistry, 42(16), 3163-3166. https://doi.org/10.1021/jm990131e