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

Abstract

Febrifugine (1) and isofebrifugine (2), isolated from the roots of Dichroa febrifuga Lour. (Chinese name: Cháng Shan), 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.

• Authors: Y Takaya, H Tasaka, T Chiba, K Uwai, M Tanitsu, H S Kim, Y Wataya, M Miura, M Takeshita, Y Oshima
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 42 Issue 16 Pg. 3163-6 (Aug 12 1999) ISSN: 0022-2623 [Print] United States
• PMID: 10447961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3-(hydroxy-4,4-dimethyl-2-oxo-3-quinolizidyl)-4-quinazolinone
• Antimalarials
• Drugs, Chinese Herbal
• Piperidines
• Quinazolines
• Quinazolinones
• Quinolizines
• febrifugine

Topics

• Animals
• Antimalarials (chemical synthesis, chemistry, isolation & purification, pharmacology)
• Drugs, Chinese Herbal (chemistry, isolation & purification, pharmacology)
• Malaria (drug therapy)
• Male
• Mice
• Mice, Inbred ICR
• Models, Molecular
• Molecular Conformation
• Piperidines
• Plasmodium berghei
• Plasmodium falciparum (drug effects)
• Quinazolines (chemical synthesis, chemistry, isolation & purification, pharmacology)
• Quinazolinones
• Quinolizines (chemical synthesis, chemistry, pharmacology)