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疟疾是热带地区致病和致死的主要原因之一,其中大多数死之病例均由恶性疟原虫所致。因疟原虫对传统抗疟药物的耐药性以惊人的速度增强,因而急需新的有效药物。磷米多霉素(Fosmidomycin)和FR-900089作为一类有潜力的新的抗疟药因其对多耐药寄生虫的良好疗效及低廉的价格和高度稳定性而倍受关注。 哺乳动物体内和真菌中类异戊二烯的生物合成依赖于不同数量异戊烯二磷酸单元的凝聚,异戊烯二磷酸又经甲羟戊酸途径产生。研究表明恶性疟原虫体内甲羟戊酸途径缺乏。最近有人提出DOXP(1-deoxy-D-xylu-lose 5-phosphate)途径:在DOXP合成酶和DOXP还原异构酶的作用下,甘油醛3-磷酸和丙酮酸凝聚成DOXP,之后DOXP转变为2-C-甲基-D-赤藓醇基-4-磷酸,为类异戊二
Malaria is one of the major causes of morbidity and mortality in the tropics, with the majority of deaths caused by Plasmodium falciparum. Due to the alarming rate of resistance of Plasmodium to traditional anti-malarial drugs, there is an urgent need for new and effective drugs. Fosmidomycin and FR-900089 have drawn great attention as a potential new anti-malaria drug because of their good efficacy against multi-resistant parasites and their low price and high stability. The biosynthesis of isoprenoids in mammals and fungi depends on the cohesion of different amounts of isopentenyl diphosphate units, which are in turn produced by the mevalonate pathway. Studies have shown a lack of mevalonate pathway in P. falciparum. Recently, a DOXP (1-deoxy-D-xylu-lose 5-phosphate) pathway has been proposed: glyceraldehyde 3-phosphate and pyruvate condense into DOXP under the action of DOXP synthase and DOXP reductoisomerase, 2-C-methyl-D-erythritol-4-phosphate, isoprenoid