Fosmidomycin

Not to be confused with Fosfomycin.
Fosmidomycin
Structural formula of fosmidomycin
Ball-and-stick model of the fosmidomycin molecule
Clinical data
ATC code none
Identifiers
CAS Number 66508-53-0 N
PubChem (CID) 572
DrugBank DB02948 YesY
ChemSpider 555 YesY
UNII 5829E3D9I9 YesY
ChEBI CHEBI:443725 YesY
ChEMBL CHEMBL203125 YesY
Chemical and physical data
Formula C4H10NO5P
Molar mass 183.100 g/mol
3D model (Jmol) Interactive image
 NYesY (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]

Use in malaria

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. doi:10.7164/antibiotics.33.18. PMID 7372546.
  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 1538678Freely accessible. PMID 16870763.
  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 2600645Freely accessible. PMID 18973702.
  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 2688282Freely accessible. PMID 19216790.
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