Double ester prodrugs of FR900098 display enhanced in-vitro antimalarial activity |
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| Authors: | Wiesner Jochen Ortmann Regina Jomaa Hassan Schlitzer Martin |
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| Affiliation: | 1. Institut für Klinische Chemie und Pathobiochemie, Universit?tsklinikum Giessen und Marburg GmbH, Gie?en, Germany;2. Institut für Pharmazeutische Chemie, Philipps‐Universit?t Marburg, Marburg, Germany. Fax: +49 6421 28‐25978 |
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| Abstract: | 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. |
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| Keywords: | 1‐Deoxy‐D‐xylulose 5‐phosphate reductoisomerase inhibitors Mevalonate‐independent isoprenoid biosynthesis Prodrug |
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