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

138 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

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Bearings (structural)
Quinolizidines
Plasmodium malariae
Antimalarials
Acetone
Parasites
Falciparum Malaria
Silica Gel
Chloroquine
Therapeutic Uses
Metabolism
Liver
Malaria
Names
Blood
Pharmaceutical Preparations
febrifugine

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

New type of febrifugine analogues, bearing a quinolizidine moiety, show potent antimalarial activity against Plasmodium malaria parasite. / Takaya, Yoshiaki; Tasaka, Hidehisa; Chiba, Tomoyuki; Uwai, Koji; Tanitsu, Masa Aki; Kim, Hye-Sook; Wataya, Yusuke; Miura, Masatomo; Takeshita, Mitsuhiro; Oshima, Yoshiteru.

In: Journal of Medicinal Chemistry, Vol. 42, No. 16, 12.08.1999, p. 3163-3166.

Research output: Contribution to journalArticle

Takaya, Y, Tasaka, H, Chiba, T, Uwai, K, Tanitsu, MA, 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, vol. 42, no. 16, pp. 3163-3166. https://doi.org/10.1021/jm990131e
Takaya, Yoshiaki ; Tasaka, Hidehisa ; Chiba, Tomoyuki ; Uwai, Koji ; Tanitsu, Masa Aki ; Kim, Hye-Sook ; Wataya, Yusuke ; Miura, Masatomo ; Takeshita, Mitsuhiro ; Oshima, Yoshiteru. / New type of febrifugine analogues, bearing a quinolizidine moiety, show potent antimalarial activity against Plasmodium malaria parasite. In: Journal of Medicinal Chemistry. 1999 ; Vol. 42, No. 16. pp. 3163-3166.
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AU - Uwai, Koji

AU - Tanitsu, Masa Aki

AU - Kim, Hye-Sook

AU - Wataya, Yusuke

AU - Miura, Masatomo

AU - Takeshita, Mitsuhiro

AU - Oshima, Yoshiteru

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