Acyloxyalkyl ester prodrugs of FR900098 with improved in vivo anti-malarial activity
| Autor: | Regina Ortmann, Ewald Beck, Jochen Wiesner, Armin Reichenberg, Martin Schlitzer, Dajana Henschker, Hassan Jomaa |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Plasmodium vinckei
Clinical Biochemistry Biological Availability Mevalonic Acid Pharmaceutical Science Biochemistry Chemical synthesis Antimalarials Mice chemistry.chemical_compound Fosfomycin Oral administration In vivo parasitic diseases Drug Discovery medicine Animals Prodrugs Molecular Biology chemistry.chemical_classification Mice Inbred BALB C Hydroxamic acid biology Organic Chemistry Prodrug biology.organism_classification Fosmidomycin Malaria Enzyme chemistry Molecular Medicine Indicators and Reagents Lysophospholipids medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 13:2163-2166 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/s0960-894x(03)00354-8 |
| Popis: | FR900098 represents an improved derivative of the new antimalarial drug fosmidomycin and acts through inhibition of the 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase, an essential enzyme of the mevalonate independent pathway of isoprenoid biosynthesis. Prodrugs with increased activity after oral administration were obtained by chemical modification of the phosphonate moiety to yield acyloxyalkyl esters. The most successful compound demonstrated 2-fold increased activity in mice infected with the rodent malaria parasite Plasmodium vinckei. |
| Databáze: | OpenAIRE |
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