Fosmidomycin for the treatment of malaria
Fosmidomycin for the treatment of malaria
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DOI：
10.1007/s00436-002-0770-9
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发表时间：
2003-06
影响因子：
2
通讯作者：
J. Wiesner;S. Borrmann;H. Jomaa
中科院分区：
文献类型：
--
作者：
J. Wiesner;S. Borrmann;H. Jomaa
在疟原虫中，类异戊二烯是通过甲羟戊酸独立的 1-脱氧-D-木酮糖 5-磷酸 (DOXP) 途径合成的。 Fosmidomycin 是一种天然抗生素，最初开发用于治疗细菌感染，是 DOXP 还原异构酶的抑制剂，DOXP 还原异构酶是该途径的必需酶。最近的临床研究表明，磷米霉素可有效治疗人类单纯性恶性疟原虫。该治疗耐受性良好，可快速清除寄生虫和发烧。然而，高复发率阻碍了膦米霉素作为单一疗法的使用。在药物组合研究中，观察到磷米霉素与克林霉素的协同作用。目前正在进行福米霉素-克林霉素组合的临床研究。
In malaria parasites, isoprenoids are synthesised by the mevalonate independent 1-deoxy-D-xylulose 5-phosphate (DOXP) pathway. Fosmidomycin, a natural antibiotic originally developed for the treatment of bacterial infections, represents an inhibitor of DOXP reductoisomerase, an essential enzyme of this pathway. In recent clinical studies it was shown that fosmidomycin is effective in curing uncomplicatedPlasmodiumfalciparummalaria in humans. The treatment was well tolerated and resulted in a fast parasite and fever clearance. However, the high rate of recrudescence precludes the use of fosmidomycin as a monotherapy. In drug combination studies, synergy of fosmidomycin with clindamycin was observed. Clinical studies with a fosmidomycin-clindamycin combination are currently ongoing.