New type of febrifugine analogues, bearing a quinolizidine moiety, show potent antimalarial activity against Plasmodium malaria parasite.
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.
Takaya
Y
Y
Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Sendai 980-8578, Japan.
Tasaka
H
H
Chiba
T
T
Uwai
K
K
Tanitsu
M
M
Kim
H S
HS
Wataya
Y
Y
Miura
M
M
Takeshita
M
M
Oshima
Y
Y
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008288:Malaria / Q000188:drug therapy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D008968:Molecular Conformation; D010880:Piperidines; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D052999:Quinazolinones; D011807:Quinolizines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C120840:3-(hydroxy-4,4-dimethyl-2-oxo-3-quinolizidyl)-4-quinazolinone; D000962:Antimalarials; D004365:Drugs, Chinese Herbal; D010880:Piperidines; D011799:Quinazolines; D052999:Quinazolinones; D011807:Quinolizines; C001207:febrifugine