Fosmidomycin

Fosmidomycin
Clinical data
ATC code	none;
Identifiers
	IUPAC name 3-[Formyl(hydroxy)amino]propylphosphonic acid;
CAS Number	66508-53-0 ;
PubChem CID	572;
DrugBank	DB02948 ;
ChemSpider	555 ;
UNII	5829E3D9I9;
ChEBI	CHEBI:443725 ;
ChEMBL	ChEMBL203125 ;
CompTox Dashboard (EPA)	DTXSID70216712 ;
Chemical and physical data
Formula	C4H10NO5P
Molar mass	183.100 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=P(O)(O)CCCN(O)C=O;
	InChI InChI=1S/C4H10NO5P/c6-4-5(7)2-1-3-11(8,9)10/h4,7H,1-3H2,(H2,8,9,10) ; Key:GJXWDTUCERCKIX-UHFFFAOYSA-N ;
	(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

^ 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.
^ 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
^ 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.
^ 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.
^ 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.
^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

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[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

[Jomaa1999-3] 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.

[Borrmann2004-4] 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.

[Borrmann2006-5] 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.

[Ruangweerayut2008-6] 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[Dharia2009-7] 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

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