Activities of new acridone alkaloid derivatives against Plasmodium yoelii in vitro.
Forty-seven new acridone alkaloid derivatives (SA compounds) were tested for antimalarial activity in vitro. At a concentration of 1.0 microgram/ml, six of these inhibited 50% or more of the incorporation of [3H]hypoxanthine into Plasmodium yoelii in vitro. The four most potent compounds, SA 3757, SA 3548, SA 3761 and SA 3499, showed 50% inhibitory concentration (IC50) values of 0.023 microgram/ml, 0.03 microgram/ml, 0.053 microgram/ml and 0.15 microgram/ml, respectively. The chemotherapeutic indexes of these four acridones, based on the ratio of the 50% lethal concentration (LC50) values for cell growth of L1210 cells to the IC50 for inhibition of uptake of [3H]hypoxanthine into P. yoelii, were calculated to be equal to or more higher (greater than 870, 263, 189 and greater than 133, respectively) than chloroquine diphosphate (315) or pyrimethamine (87).
Fujioka
H
H
Department of Medical Zoology, Nagoya University School of Medicine, Japan.
Kato
N
N
Fujita
M
M
Fujimura
K
K
Nishiyama
Y
Y
D000166:Acridines / Q000737:chemistry / Q000494:pharmacology*; D054831:Acridones; D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D004912:Erythrocytes / Q000469:parasitology; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000473:pathology; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010967:Plasmodium yoelii / Q000187:drug effects*; D011739:Pyrimethamine / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000166:Acridines; D054831:Acridones; D000470:Alkaloids; D000962:Antimalarials; C041300:acridone; D002738:Chloroquine; D011739:Pyrimethamine