Fowler R E, Sinden R E, Pudney M
Department of Biology, Imperial College of Science, Technology and Medicine, London, United Kingdom.
J Parasitol. 1995 Jun;81(3):452-8.
Ookinete formation from mature Plasmodium berghei gametocytes in vitro was partially inhibited by 0.05-0.1 microM atovaquone and almost totally blocked at a concentration of 0.25 microM. Microgametocyte exflagellation was not affected by atovaquone at concentrations up to 300 microM. Ookinete formation was also inhibited in culture when addition of 0.20 microM atovaquone was delayed by 4 hr, by which time DNA replication was likely to have been completed. Inhibition of ookinete formation by atovaquone was not reversed by orotic acid. Plasmodium berghei-infected Anopheles stephensi mosquitoes were fed a second blood meal 4, 7, 14, and 20 days postinfection (p.i.) from mice that had been treated with atovaquone or control diluent 8 hr previously. Atovaquone blood feeds on day 4 reduced oocyst numbers on days 6-12, although sporozoite numbers in the thorax and abdomen on day 20 were not significantly reduced. Blood feeds on day 7 slowed oocyst growth, blood feeds on day 14 did not significantly reduce sporozoite numbers, and feeds to mosquitoes on day 20 p.i. had no effect on transmission to naive mice. Sporozoite invasion of human hepatoma cells was unaffected by the presence of atovaquone.
体外培养时，0.05 - 0.1微摩尔的阿托伐醌可部分抑制伯氏疟原虫成熟配子体形成动合子，浓度为0.25微摩尔时几乎完全阻断动合子形成。浓度高达300微摩尔的阿托伐醌对小配子体的出丝现象没有影响。当阿托伐醌的添加延迟4小时时（此时DNA复制可能已经完成），体外培养的动合子形成也受到抑制。乳清酸不能逆转阿托伐醌对动合子形成的抑制作用。在感染伯氏疟原虫的斯氏按蚊感染后4、7、14和20天，给其喂食来自8小时前用阿托伐醌或对照稀释剂处理过的小鼠的第二次血餐。感染后第4天喂食阿托伐醌可减少感染后6 - 12天的卵囊数量，不过感染后第20天胸部和腹部的子孢子数量没有显著减少。感染后第7天喂食可减缓卵囊生长，感染后第14天喂食对减少子孢子数量没有显著作用，感染后第20天给蚊子喂食对向未感染小鼠的传播没有影响。阿托伐醌的存在不影响子孢子对人肝癌细胞的侵袭。
