New type of febrifugine analogues, bearing a quinolizidine moiety, show potent antimalarial activity against Plasmodium malaria parasite
New type of febrifugine analogues, bearing a quinolizidine moiety, show potent antimalarial activity against Plasmodium malaria parasite
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DOI：
10.1021/jm990131e
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发表时间：
1999-08-12
影响因子：
7.3
通讯作者：
Oshima, Y
中科院分区：
文献类型：
--
作者：
Takaya, Y;Tasaka, H;Oshima, Y
从中药常山（Dichroa febrifuga Lour.）（中文名：常山），是抗疟疾的有效成分。使用硅胶和丙酮分别获得1和2与丙酮的加合物Df-1（3）和Df-2（4）。它们在体外对恶性疟原虫疟疾表现出高活性。发现化合物3与临床使用的药物氯喹在体内对伯氏疟原虫同样有效，而4仅显示出3的1/24的活性。这些化合物的代谢研究表明，化合物4在小鼠肝脏中易于代谢。因此，4的剂量必须高于3的剂量，以达到足以产生有利治疗效果的血液水平。
Febrifugine (1) and isofebrifugine (2), isolated from the roots of Dichroa febrifuga Lour. (Chinese name: Chang Shan), are active principles against malaria. Adducts of 1 and 2 with acetone, Df-l (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.