Fosmidomycin

Not to be confused with Fosfomycin.
Fosmidomycin
Systematic (IUPAC) name
3-[Formyl(hydroxy)amino]propylphosphonic acid
Clinical data
Pregnancy cat.  ?
Legal status  ?
Identifiers
CAS number 66508-53-0
ATC code None
PubChem CID 572
DrugBank EXPT01469
ChemSpider 555 Y
UNII 5829E3D9I9 Y
ChEBI CHEBI:443725 Y
ChEMBL CHEMBL203125 Y
Chemical data
Formula C4H10NO5P 
Mol. mass 183.100 g/mol
SMILES eMolecules & PubChem
 Y(what is this?)  (verify)

Fosmidomycin is an antibiotic that was originally isolated from culture broths of bacteria of the genus Streptomyces.[1] It specifically inhibits DXP reductoisomerase, a key enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. It is a structural analogue of 2-C-methyl-D-erythrose 4-phosphate. It inhibits the E. coli enzyme with a KI value of 38 nM (4), MTB at 80 nM, and the Francisella enzyme at 99 nM.[2]

The discovery of the non-mevalonate pathway in malaria parasites has indicated the use of fosmidomycin and other such inhibitors as antimalarial drugs.[3] Indeed, fosmidomycin has been tested in combination treatment with clindamycin for treatment of malaria with favorable results.[4][5][6] It has been shown that an increase in copy number of the target enzyme (DXP reductoisomerase) correlates with in vitro fosmidomycin resistance in the lethal malaria parasite, Plasmodium falciparum.[7]

References

  1. ^ Iguchi, E; Okuhara, M, Kohsaka, M, Aoki, H, Imanaka, H (1980). "Studies on new phosphonic acid antibiotics. II. Taxonomic studies on producing organisms of the phosphonic acid and related compounds.". The Journal of antibiotics 33 (1): 19–23. PMID 7372546. http://www.journalarchive.jst.go.jp/japanese/jnlabstract_ja.php?cdjournal=antibiotics1968&cdvol=33&noissue=1&startpage=18. 
  2. ^ Jawaid, S., Seidle, H., Zhou W, Abdirahman, H., Abadeer, M, Hix, JH, van Hoek, ML and RD Couch. Kinetic Characterization and Phosphoregulation of the Francisella tularensis 1-Deoxy-D-Xylulose 5-Phosphoate Reductoisomerase (MEP Synthase), PLOS One, 4(12): e8288. doi:10.1371/journal.pone.0008288
  3. ^ Jomaa, H; et al. (1999). "Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs". Science 285 (5433): 1573–6. doi:10.1126/science.285.5433.1573. PMID 10477522. 
  4. ^ Borrmann, S; et al. (2004). "Fosmidomycin-clindamycin for Plasmodium falciparum infections in African children". J Infect Dis 189 (5): 901–8. doi:10.1086/381785. PMID 14976608. 
  5. ^ Borrmann, S; et al. (2006). "Fosmidomycin plus clindamycin for treatment of pediatric patients aged 1 to 14 years with Plasmodium falciparum malaria". Antimicrob Agents Chemother 50 (8): 2713–8. doi:10.1128/AAC.00392-06. PMC 1538678. PMID 16870763. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1538678. 
  6. ^ Ruangweerayut, R; et al. (2008). "Assessment of the pharmacokinetics and dynamics of two combination regimens of fosmidomycin-clindamycin in patients with acute uncomplicated falciparum malaria". Malaria J 7 (1): 225. doi:10.1186/1475-2875-7-225. PMC 2600645. PMID 18973702. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2600645. 
  7. ^ Dharia, NV; et al. (2009). "Use of high-density tiling microarrays to globally identify mutations and elucidate mechanisms of drug resistance in Plasmodium falciparum". Genome Biology 10 (2): R21. doi:10.1186/gb-2009-10-2-r21. PMC 2688282. PMID 19216790. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2688282.