Fumagillin is a complex

biomolecule A biomolecule or biological molecule is a loosely used term for molecules present in organisms that are essential to one or more typically biological processes, such as cell division, morphogenesis, or developmental biology, development. Biom ...

and used as an

antimicrobial An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals ar ...

agent. It was isolated in 1949 from the microbial organism ''

Aspergillus fumigatus ''Aspergillus fumigatus'' is a species of fungus in the genus '' Aspergillus'', and is one of the most common ''Aspergillus'' species to cause disease in individuals with an immunodeficiency. ''Aspergillus fumigatus'', a saprotroph widespread i ...

''.

Uses

In animals

It was originally used against microsporidian parasites ''

Nosema apis ''Nosema apis'' is a microsporidian, a small, unicellular parasite recently reclassified as a fungus that mainly affects honey bees. It causes nosemosis, also called nosema, which is the most common and widespread of adult honey bee diseases. T ...

'' infections in

honey bee A honey bee (also spelled honeybee) is a eusocial flying insect within the genus ''Apis'' of the bee clade, all native to Afro-Eurasia. After bees spread naturally throughout Africa and Eurasia, humans became responsible for the current cosm ...

s. Some studies found it to be effective against some

myxozoa Myxozoa (etymology: Greek: μύξα ''myxa'' "slime" or "mucus" + thematic vowel o + ζῷον ''zoon'' "animal") is a subphylum of aquatic cnidarian animals – all obligate parasites. It contains the smallest animals ever known to have lived. O ...

parasite Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson h ...

s, including ''

Myxobolus cerebralis ''Myxobolus cerebralis'' is a myxosporean parasite of salmonids (salmon and trout species) that causes whirling disease in farmed salmon and trout and also in wild fish populations. It was first described in rainbow trout in Germany in 1893, ...

,'' an important parasite of

fish Fish are Aquatic animal, aquatic, craniate, gill-bearing animals that lack Limb (anatomy), limbs with Digit (anatomy), digits. Included in this definition are the living hagfish, lampreys, and Chondrichthyes, cartilaginous and bony fish as we ...

; however, in the more rigorous tests required for U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

approval, it was ineffective. There are reports that fumagillin controls ''

Nosema ceranae ''Nosema ceranae'' is a microsporidian, a small, unicellular parasite that mainly affects ''Apis cerana'', the Asiatic honey bee. Along with '' Nosema apis'', it causes the disease nosemosis, the most widespread of the diseases of adult honey b ...

'', which has recently been hypothesized as a possible cause of

colony collapse disorder Colony collapse disorder (CCD) is an abnormal phenomenon that occurs when the majority of worker bees in a honey bee colony disappear, leaving behind a queen, plenty of food, and a few nurse bees to care for the remaining immature bees. While s ...

. The latest report, however, has shown it to be ineffective against ''N. ceranae''. Fumagillin is also investigated as an inhibitor of

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. ...

parasite growth.

In humans

Fumagillin has been used in the treatment of

microsporidiosis Microsporidiosis is an opportunistic intestinal infection that causes diarrhea and wasting in immunocompromised individuals ( HIV, for example). It results from different species of microsporidia, a group of microbial (unicellular) fungi. In HI ...

. It is also an

amebicide An amebicide (or amoebicide) is an agent that is destructive to amoeba, especially parasitic amoeba that cause amoebiasis. Entamoeba * Metronidazole, or a related drug such as Tinidazole, Secnidazole or Ornidazole, is used to destroy amoebae that ...

. Fumagillin can block blood vessel formation by binding to an enzyme methionine aminopeptidase 2 and for this reason, the compound, together with semisynthetic derivatives, are investigated as an

angiogenesis inhibitor An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels ( angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical ...

in the treatment of cancer. The company Zafgen conducted clinical trials using the fumagillin

analog Analog or analogue may refer to: Computing and electronics * Analog signal, in which information is encoded in a continuous variable ** Analog device, an apparatus that operates on analog signals *** Analog electronics, circuits which use analog ...

beloranib Beloranib is a former drug candidate for the treatment of obesity. It was discovered by CKD Pharmaceuticals and its clinical development was led by Zafgen. Drug development was halted in 2016 after deaths during clinical trials. Mechanism of ac ...

for weight loss, but they were unsuccessful. Fumagillin is toxic to

erythrocyte Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "hol ...

s ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...

'' at concentrations greater than 10 μM.

Total synthesis

Fumagillin and the related fumagillol (the hydrolysis product) have been a target in

total synthesis Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes i ...

, with several reported successful strategies, racemic, asymmetric, and formal.

References

{{Agents against amoebozoa Western honey bee medications Epoxides Antiprotozoal agents Total synthesis