Fumagillin

Source: Wikipedia, the free encyclopedia.
Fumagillin
QP51AX23 (WHO
)
Identifiers
  • (2E,4E,6E,8E)-10-{[(3R,4S,5S,6R)-5-methoxy- 4-[(2R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1- oxaspiro[2.5]octan-6-yl]oxy}-10 -oxodeca-2,4,6,8-tetraenoic acid
JSmol)
  • CC(=CC[C@@H]1[C@@](O1)(C)[C@H]2[C@@H]([C@@H](CC[C@]23CO3)OC(=O)/C=C/C=C/C=C/C=C/C(=O)O)OC)C
  • InChI=1S/C26H34O7/c1-18(2)13-14-20-25(3,33-20)24-23(30-4)19(15-16-26(24)17-31-26)32-22(29)12-10-8-6-5-7-9-11-21(27)28/h5-13,19-20,23-24H,14-17H2,1-4H3,(H,27,28)/b7-5+,8-6+,11-9+,12-10+/t19-,20-,23-,24-,25+,26+/m1/s1 ☒N
  • Key:NGGMYCMLYOUNGM-CSDLUJIJSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

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

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. PMID 18550078
    .
  3. ^ Sabin Russell (2007-04-26). "UCSF scientist tracks down suspect in honeybee deaths". San Francisco Chronicle.
  4. ^ "Scientists Identify Pathogens That May Be Causing Global Honeybee Deaths" (PDF). Edgewood Chemical Biological Center. 2007-04-25.[verification needed]
  5. PMID 23505365
    .
  6. PMID 19246010
    .
  7. PMID 19648008
    .
  8. S2CID 205423324
    .
  9. PMID 12075057
    .
  10. S2CID 41794515
    .
  11. ^ Gilbert MA, Granath WO (August 2003). "Whirling disease of salmonid fish: life cycle, biology, and disease". The Journal of Parasitology. 89 (4): 658–667.
    S2CID 8950955
    .
  12. S2CID 1020594
    .
  13. ^ "Zafgen Announces Positive Topline Phase 1b Data for ZGN-433 in Obesity". MedNews. Drugs.com. 5 January 2011.
  14. ^ "Zafgen Halts Development of Beloranib, to Cut Jobs by ~34%". nasdaq.com. July 20, 2016.
  15. PMID 23121865
    .
  16. PMID 5016935
    .
  17. doi:10.1016/S0040-4039(97)00925-8
    .
  18. PMID 29711854
    .
  19. S2CID 196782462
    .
  20. S2CID 95897985
    .
  21. PMID 11506622
    .
  22. doi:10.1002/ejoc.200400262
    .
  23. PMID 16365904
    .
  24. PMID 20209516
    .
Retrieved from "https://en.wikipedia.org/w/index.php?title=Fumagillin&oldid=1189160497"