FR900098的双酯前药显示出增强的体外抗疟活性。
Double ester prodrugs of FR900098 display enhanced in-vitro antimalarial activity.
作者信息
Wiesner Jochen, Ortmann Regina, Jomaa Hassan, Schlitzer Martin
机构信息
Institut für Klinische Chemie und Pathobiochemie, Universitätsklinikum Giessen und Marburg GmbH, Giessen, Germany.
出版信息
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。
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