Wiesner Jochen, Ortmann Regina, Jomaa Hassan, Schlitzer Martin
Institut für Klinische Chemie und Pathobiochemie, Universitätsklinikum Giessen und Marburg GmbH, Giessen, Germany.
Arch Pharm (Weinheim). 2007 Dec;340(12):667-9. doi: 10.1002/ardp.200700069.
Fosmidomycin and FR900098 are inhibitors of the 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR; IspC), a key enzyme of the mevalonate-independent isoprenoid biosynthesis pathway. We have determined the in-vitro antimalarial activity of two double ester prodrugs 2, 3 in direct comparison with the unmodified FR900098 1 against intraerythrocytic forms of Plasmodium falciparum. Temporarily masking the polar properties of the phosphonate moiety of the DXR inhibitor FR900098 1 enhanced not only its oral bioavailability but also the intrinsic activity of this series against the parasites.
磷霉素和FR900098是1-脱氧-D-木酮糖5-磷酸还原异构酶（DXR；IspC）的抑制剂，DXR是甲羟戊酸非依赖性类异戊二烯生物合成途径的关键酶。我们已直接比较了两种双酯前药2、3与未修饰的FR900098 1对恶性疟原虫红细胞内形式的体外抗疟活性。暂时掩盖DXR抑制剂FR900098 1的膦酸酯部分的极性特性，不仅提高了其口服生物利用度，还增强了该系列对寄生虫的内在活性。
