Journal
ARCHIV DER PHARMAZIE
Volume 338, Issue 7, Pages 305-314Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/ardp.200500976
Keywords
malaria; prodrug; Plasmodium falciparum; isoprenoid biosynthesis
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FR900098 represents a derivative of the new antimalarial drug fosmidomycin with enhanced activity. The mechanism of action is the inhibition of the 1-desoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase, an essential enzyme of the mevalonate independent pathway of isoprenoid biosynthesis. Prodrugs with increased oral activity in mice infected with the rodent malaria parasite Plasmodium vinckei were obtained by masking the phosphonate moiety of FR900098 as alkoxycarbonyloxyethyl esters.
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