Peters W, Robinson B L, Rossier J C, Jefford C W
CAB International Institute of Parasitology, St. Albans, Hertfordshire, U.K.
Ann Trop Med Parasitol. 1993 Feb;87(1):1-7. doi: 10.1080/00034983.1993.11812733.
The new Chinese antimalarial blood schizontocide, artemisinin, derived from the plant Artemisia annua, displays a high level of activity against polyresistant Plasmodium falciparum. Several synthetic 1,2,4-trioxanes were examined in a search for compounds that exhibit a similar type of action against drug-resistant parasites. This paper, the first of a series, describes the examination of these trioxanes against drug-sensitive and drug-resistant malaria parasites in a rodent model, using artemisinin and arteether as comparison standards. Cis-fused cyclohexeno-1,2,4-trioxanes (10-17) substituted with various side-chains revealed for the most part variable but weak antimalarial activity. On the other hand, cis-fused cyclopenteno-1,2,4-trioxanes (18-19) showed greater activity, 19 showing about 1/30th of the activity of arteether against drug-sensitive Plasmodium berghei in vivo, thereby providing a clue to the structure-activity relationship.
源自植物青蒿的新型中国抗疟血液裂殖体杀灭剂青蒿素，对多重耐药的恶性疟原虫显示出高度活性。为寻找对耐药寄生虫表现出类似作用类型的化合物，对几种合成的1,2,4 -三恶烷进行了研究。本系列论文的第一篇描述了在啮齿动物模型中，以青蒿素和蒿乙醚作为比较标准，对这些三恶烷针对药物敏感和耐药疟原虫的研究。用各种侧链取代的顺式稠合环己烯 - 1,2,4 -三恶烷（10 - 17）大多显示出可变但较弱的抗疟活性。另一方面，顺式稠合环戊烯 - 1,2,4 -三恶烷（18 - 19）表现出更大的活性，其中19在体内对药物敏感的伯氏疟原虫的活性约为蒿乙醚的1/30，从而为构效关系提供了线索。
