Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
J Med Chem. 2012 Sep 13;55(17):7892-9. doi: 10.1021/jm3009986. Epub 2012 Aug 27.
In only three steps and in 21-67% overall yields from the natural trioxane artemisinin, a series of 21 new trioxane C-10 thioacetals was prepared. Upon receiving a single oral dose of only 6 mg/kg of the monomeric trioxane 12c combined with 18 mg/kg of mefloquine hydrochloride, Plasmodium berghei-infected mice survived on average 29.8 days after infection. Two of the four mice in this group had no parasites detectable in their blood on day 30 after infection, and they behaved normally and appeared healthy. One of the mice had 11% blood parasitemia on day 30, and one mouse in this group died on day 29. Of high medicinal importance, the efficacy of this ACT chemotherapy is much better than (almost double) the efficacy under the same conditions using as a positive control the popular trioxane drug artemether plus mefloquine hydrochloride (average survival time of only 16.5 days).
仅需三个步骤，即可从天然三氧杂环丙烷青蒿素中获得 21-67%的总收率，我们合成了一系列 21 种新型三氧杂环丙烷 C-10 硫缩醛。感染疟原虫伯氏疟原虫的小鼠在经口给予 6 毫克/千克的单体三氧杂环丙烷 12c 与 18 毫克/千克盐酸甲氟喹的单一剂量后，平均存活时间为感染后 29.8 天。在该组的 4 只小鼠中，有 2 只在感染后 30 天血液中已检测不到寄生虫，它们行为正常，看起来健康。其中一只小鼠在第 30 天的血液寄生虫率为 11%，而该组中的一只小鼠在第 29 天死亡。具有重要药用价值的是，这种 ACT 化疗的疗效远远优于（几乎是两倍）在相同条件下使用作为阳性对照的流行三氧杂环丙烷药物青蒿琥酯加盐酸甲氟喹的疗效（平均存活时间仅为 16.5 天）。
