Chemistry:Fumagillin

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Short description: Chemical compound
Fumagillin
Fumagillin structure.svg
Clinical data
AHFS/Drugs.comInternational Drug Names
ATC code
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CAS Number
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Chemical and physical data
FormulaC26H34O7
Molar mass458.551 g·mol−1
3D model (JSmol)
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Fumagillin is a complex biomolecule and used as an antimicrobial agent. It was isolated in 1949 from the microbial organism Aspergillus fumigatus.[1]

Uses

In animals

It was originally used against microsporidian parasites Nosema apis infections in honey bees.[citation needed]

Some studies found it to be effective against some myxozoan parasites, including Myxobolus cerebralis, an important parasite of fish; however, in the more rigorous tests required for U.S. Food and Drug Administration approval, it was ineffective.[citation needed]

There are reports that fumagillin controls Nosema ceranae,[2] which has recently been hypothesized as a possible cause of colony collapse disorder.[3][4] The latest report, however, has shown it to be ineffective against N. ceranae.[5] Fumagillin is also investigated as an inhibitor of malaria parasite growth.[6][7]

In humans

Fumagillin has been used in the treatment of microsporidiosis.[8][9] It is also an amebicide.[10]

Fumagillin can block blood vessel formation by binding to an enzyme methionine aminopeptidase 2[11] and for this reason, the compound, together with semisynthetic derivatives, are investigated as an angiogenesis inhibitor[12] in the treatment of cancer.

The company Zafgen conducted clinical trials using the fumagillin analog beloranib for weight loss,[13] but they were unsuccessful.[14]

Fumagillin is toxic to erythrocytes in vitro at concentrations greater than 10 μM.[15]

Total synthesis

Fumagillin and the related fumagillol (the hydrolysis product) have been a target in total synthesis, with several reported successful strategies, racemic, asymmetric, and formal.[16][17][18][19][20][21][22][23][24]

References

  1. F. R. Hanson, T. E. Elbe, J. Bacteriol. 1949, 58, 527
  2. "Does fumagillin control the recently detected invasive parasite Nosema ceranae in western honey bees (Apis mellifera)?". Journal of Invertebrate Pathology 99 (3): 342–344. November 2008. doi:10.1016/j.jip.2008.04.005. PMID 18550078. 
  3. Sabin Russell (2007-04-26). "UCSF scientist tracks down suspect in honeybee deaths". San Francisco Chronicle. http://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2007/04/26/MNGK7PFOMS1.DTL. 
  4. "Scientists Identify Pathogens That May Be Causing Global Honeybee Deaths". Edgewood Chemical Biological Center. 2007-04-25. http://www.ecbc.army.mil/pr/download/042507_honey_bee_pathogens.pdf. [verification needed]
  5. "Nosema ceranae escapes fumagillin control in honey bees". PLOS Pathogens 9 (3): e1003185. March 2013. doi:10.1371/journal.ppat.1003185. PMID 23505365. 
  6. "Fumagillin and fumarranol interact with P. falciparum methionine aminopeptidase 2 and inhibit malaria parasite growth in vitro and in vivo". Chemistry & Biology 16 (2): 193–202. February 2009. doi:10.1016/j.chembiol.2009.01.006. PMID 19246010. 
  7. Christopher Arico-Muendel et al. "Antiparasitic activities of novel, orally available fumagillin analogs". Bioorganic & Medicinal Chemistry Letters Vol. 19 Nr. 17 (2009), blz. 5128-5131 "Antiparasitic activities of novel, orally available fumagillin analogs". Bioorganic & Medicinal Chemistry Letters 19 (17): 5128–5131. September 2009. doi:10.1016/j.bmcl.2009.07.029. PMID 19648008. 
  8. "Microsporidiosis in solid organ transplant recipients: two Enterocytozoon bieneusi cases and review". Transplant Infectious Disease 11 (1): 83–88. February 2009. doi:10.1111/j.1399-3062.2008.00347.x. PMID 18803616. 
  9. "Fumagillin treatment of intestinal microsporidiosis". The New England Journal of Medicine 346 (25): 1963–1969. June 2002. doi:10.1056/NEJMoa012924. PMID 12075057. 
  10. "Fumagillin: an anti-infective as a parent molecule for novel angiogenesis inhibitors". Expert Review of Anti-Infective Therapy 5 (4): 573–579. August 2007. doi:10.1586/14787210.5.4.573. PMID 17678422. 
  11. "Whirling disease of salmonid fish: life cycle, biology, and disease". The Journal of Parasitology 89 (4): 658–667. August 2003. doi:10.1645/GE-82R. PMID 14533670. 
  12. "Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth". Nature 348 (6301): 555–557. December 1990. doi:10.1038/348555a0. PMID 1701033. Bibcode1990Natur.348..555I. 
  13. "Zafgen Announces Positive Topline Phase 1b Data for ZGN-433 in Obesity". MedNews. Drugs.com. 5 January 2011. https://www.drugs.com/clinical_trials/zafgen-announces-positive-topline-phase-1b-data-zgn-433-obesity-10955.html. 
  14. "Zafgen Halts Development of Beloranib, to Cut Jobs by ~34%". nasdaq.com. July 20, 2016. http://www.nasdaq.com/article/zafgen-halts-development-of-beloranib-to-cut-jobs-by-34-cm651992. 
  15. "Stimulation of suicidal erythrocyte death by fumagillin". Basic & Clinical Pharmacology & Toxicology 112 (5): 346–351. May 2013. doi:10.1111/bcpt.12033. PMID 23121865. 
  16. "A total synthesis of (+-)-fumagillin". Journal of the American Chemical Society 94 (7): 2549–2550. April 1972. doi:10.1021/ja00762a080. PMID 5016935. 
  17. "An asymmetric total synthesis of (−)-fumagillol". Tetrahedron Letters 38 (25): 4437–4440. 1997. doi:10.1016/S0040-4039(97)00925-8. 
  18. "A Concise Synthesis of Fumagillol". Angewandte Chemie 38 (7): 971–974. April 1999. doi:10.1002/(SICI)1521-3773(19990401)38:7<971::AID-ANIE971>3.0.CO;2-W. PMID 29711854. 
  19. "A Concise Synthesis of Fumagillol". Synlett 2001 (5): 0661–0663. 2001. doi:10.1055/s-2001-13359. 
  20. "Synthesis of (−)-Fumagillin". Journal of the American Chemical Society 121 (23): 5589. 1999. doi:10.1021/ja990784k. 
  21. "A new, ring closing metathesis-based synthesis of (-)-fumagillol". Organic Letters 3 (17): 2737–2740. August 2001. doi:10.1021/ol016343z. PMID 11506622. 
  22. "A Stereoselective Formal Synthesis of (−)-Fumagillol". European Journal of Organic Chemistry 2004 (18): 3813. 2004. doi:10.1002/ejoc.200400262. 
  23. "Concise enantio- and diastereoselective total syntheses of fumagillol, RK-805, FR65814, ovalicin, and 5-demethylovalicin". Angewandte Chemie 45 (5): 789–793. January 2006. doi:10.1002/anie.200502826. PMID 16365904. 
  24. "Syntheses of fumagillin and ovalicin". Chemistry 16 (13): 3884–3901. April 2010. doi:10.1002/chem.200902433. PMID 20209516.