疟疾：仅需一剂药物就可治愈受感染的小鼠

研究者使用一种长效的合成药物已经治愈了疟疾感染的小鼠，这种药物是在一种古老的中国民间草药的基础上加工完成的。
 
此研究小组同时研发了其他几种药方，使用这些药方三次口服剂量后就可治愈啮齿类动物的发热性疾病。这些过氧化物成分，含有关键的氧-氧作用单位，不仅比当今最好的疟疾治疗药物的效果还要好，而且更加安全。研究团队领队Gary Posner解释道。Posner教授是霍普金斯大学的化学教授。

这种古老的过氧化物抗疟药疗效很快。这种药物的主要成分是青缟素。几千年来，一直用于治疗疟疾和多种发热疾病。
 
过氧化物成分中的氧-氧单位导致疟疾寄生虫自我破坏。疟原虫可以破坏血红蛋白、红细胞携氧单位，破坏后的红细胞释放出含铁血红素，一种深红色的含铁血液色素成分，当含铁血红素遇上过氧化物，将会发生一种剧烈的化学反应，释放一种无碳的激动剂和氧化物质，最终可杀死寄生虫。

第一代药物有很多缺点，包括半衰期短于一小时。Posner和其团队会逐渐改善这些缺点。“我们这种半-合成的药物已经克服了第一代药物的很多缺点。” Posner教授说，“最重要的是这些成分疗效所持续的时间，但根据我们的设计，这些药物在体内具有更长的半衰期。我们在设计时使这些药物变得更具亲脂性，这意味着药物在脂肪中的溶解能力更强并且能迅速到达疟原虫感染的血红细胞。”

除外，新的药物通过代谢不会降解为毒性物质，与传统的配方相比更加具有安全性。 
 

Malaria: Infected Mice Cured By One Dose of New Drug

Researchers have cured malaria-infected mice with single shots of a new series of potent, long lasting synthetic drugs modelled on an ancient Chinese herbal folk remedy.01/06/2007The team also has developed several other compounds which defeated the febrile disease in rodents after three oral doses. These peroxide compounds, containing a crucial oxygen-oxygen unit, promise not only to be more effective than today’s best malaria remedies, but also potentially safer and more efficient, said research team leader Gary Posner, Scowe Professor of Chemistry in the Krieger School of Arts and Sciences at Johns Hopkins. 
"Older drugs in this family of peroxide antimalarials also are known to be fast-acting, but they are unfortunately short-lived and not curative when used by themselves," Posner said. The peroxide compounds, called trioxanes mimic artemisinin, the active agent in a Chinese herbal drug used to treat malaria and other fevers for thousands of years.

The oxygen-oxygen unit in the peroxides causes malaria parasites essentially to self-destruct. The parasites digest hemoglobin, the oxygen-carrying pigment of red blood cells, and, in the process, release a substance called heme, a deep-red iron-containing blood pigment. When the heme encounters peroxides, a powerful chemical reaction occurs, releasing carbon-free radicals and oxidizing agents that eventually kill the parasites.

The first generation of trioxane drugs had a number of shortcomings, including a half-life of less than one hour. Posner and team believe that their new compounds address those disadvantages. "Our semi-synthetic artemisinin-derived compounds successfully overcome the disadvantages of their first-generation predecessors," he said. "Most important is their curative activity after a single, low dose, which is distinctly unusual. But based on our intentional design, they may also have a longer half-life in animals. We also designed them to be more lipophilic, meaning they have an enhanced ability to dissolve in fats and thus to arrive inside malaria-infected red blood cells."

In addition, the new compounds are far less likely to break down into toxic substances when they are metabolized in the test animals’ bodies, making them potentially safer than their predecessors.