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| ECHA InfoCard | 100.041.288 |
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| Formula | C26H34O7 |
| Molar mass | 458.551 g·mol−1 |
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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]
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]
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]
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]
Plasmodium falciparum is a unicellular protozoan parasite of humans, and the deadliest species of Plasmodium that causes malaria in humans. The parasite is transmitted through the bite of a female Anopheles mosquito and causes the disease's most dangerous form, falciparum malaria. It is responsible for around 50% of all malaria cases. P. falciparum is therefore regarded as the deadliest parasite in humans. It is also associated with the development of blood cancer and is classified as a Group 2A (probable) carcinogen.
Ivermectin is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, today it is used to treat infestations including head lice, scabies, river blindness (onchocerciasis), strongyloidiasis, trichuriasis, ascariasis and lymphatic filariasis. It works through many mechanisms to kill the targeted parasites, and can be taken orally, or applied to the skin for external infestations. It belongs to the avermectin family of medications.
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. The dormant stage of N. apis is a long-lived spore which is resistant to temperature extremes and dehydration, and cannot be killed by freezing the contaminated comb. Nosemosis is a listed disease with the Office International des Epizooties (OIE).
Proguanil, also known as chlorguanide and chloroguanide, is a medication used to treat and prevent malaria. It is often used together with chloroquine or atovaquone. When used with chloroquine the combination will treat mild chloroquine resistant malaria. It is taken by mouth.
Fosmidomycin is an antibiotic that was originally isolated from culture broths of bacteria of the genus Streptomyces. 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. Several mutations in the E. coli DXP reductoisomerase were found to confer resistance to fosmidomycin.
Microsporidiosis is an opportunistic intestinal infection that causes diarrhea and wasting in immunocompromised individuals. It results from different species of microsporidia, a group of microbial (unicellular) fungi.
Helenalin, or (-)-4-Hydroxy-4a,8-dimethyl-3,3a,4a,7a,8,9,9a-octahydroazuleno[6,5-b]furan-2,5-dione, is a toxic sesquiterpene lactone which can be found in several plants such as Arnica montana and Arnica chamissonis Helenalin is responsible for the toxicity of the Arnica spp. Although toxic, helenalin possesses some in vitro anti-inflammatory and anti-neoplastic effects. Helenalin can inhibit certain enzymes, such as 5-lipoxygenase and leukotriene C4 synthase. For this reason the compound or its derivatives may have potential medical applications.
Antiparasitics are a class of medications which are indicated for the treatment of parasitic diseases, such as those caused by helminths, amoeba, ectoparasites, parasitic fungi, and protozoa, among others. Antiparasitics target the parasitic agents of the infections by destroying them or inhibiting their growth; they are usually effective against a limited number of parasites within a particular class. Antiparasitics are one of the antimicrobial drugs which include antibiotics that target bacteria, and antifungals that target fungi. They may be administered orally, intravenously or topically.
Malaria antigen detection tests are a group of commercially available rapid diagnostic tests of the rapid antigen test type that allow quick diagnosis of malaria by people who are not otherwise skilled in traditional laboratory techniques for diagnosing malaria or in situations where such equipment is not available. There are currently over 20 such tests commercially available. The first malaria antigen suitable as target for such a test was a soluble glycolytic enzyme Glutamate dehydrogenase. None of the rapid tests are currently as sensitive as a thick blood film, nor as cheap. A major drawback in the use of all current dipstick methods is that the result is essentially qualitative. In many endemic areas of tropical Africa, however, the quantitative assessment of parasitaemia is important, as a large percentage of the population will test positive in any qualitative assay.
A malaria vaccine is a vaccine that is used to prevent malaria. The only approved malaria vaccine is RTS,S, known by the brand name Mosquirix. As of April 2022, the vaccine has been given to 1 million children living in areas with moderate-to-high malaria transmission. It requires at least three doses in infants by age 2, with a fourth dose extending the protection for another 1-2 years. The vaccine reduces hospital admissions from severe malaria by around 30%.
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 bees. N. ceranae can remain dormant as a long-lived spore which is resistant to temperature extremes and dehydration. This fungus has been shown to act in a synergistic fashion with diverse insecticides such as fipronil or neonicotinoids, by increasing the toxicity of pesticides for bees, leading to higher bee mortality. It may thus play an indirect role in colony collapse disorder. In addition, the interaction between fipronil and N. ceranae induces changes in male physiology leading to sterility.
Methionine aminopeptidase 2 is an enzyme that in humans is encoded by the METAP2 gene.
The history of malaria extendes from its prehistoric origin as a zoonotic disease in the primates of Africa through to the 21st century. A widespread and potentially lethal human infectious disease, at its peak malaria infested every continent except Antarctica. Its prevention and treatment have been targeted in science and medicine for hundreds of years. Since the discovery of the Plasmodium parasites which cause it, research attention has focused on their biology as well as that of the mosquitoes which transmit the parasites.
Haemozoin is a disposal product formed from the digestion of blood by some blood-feeding parasites. These hematophagous organisms such as malaria parasites, Rhodnius and Schistosoma digest haemoglobin and release high quantities of free heme, which is the protein component of haemoglobin. Heme is a prosthetic group consisting of an iron atom contained in the center of a heterocyclic porphyrin ring. Free heme is toxic to cells, so the parasites convert it into an insoluble crystalline form called hemozoin. In malaria parasites, hemozoin is often called malaria pigment.
PfATP6, also known as PfSERCA or PfATPase6, is a calcium ATPase gene encoded by the malaria parasite Plasmodium falciparum. The protein is thought to be a P-type ATPase involved in calcium ion transport.
Zaprinast was an unsuccessful clinical drug candidate that was a precursor to the chemically related PDE5 inhibitors, such as sildenafil (Viagra), which successfully reached the market. It is a phosphodiesterase inhibitor, selective for the subtypes PDE5, PDE6, PDE9 and PDE11. IC50 values are 0.76, 0.15, 29.0, and 12.0 μM, respectively.
Atovaquone/proguanil, sold under the brand name Malarone among others, is a fixed-dose combination medication used to treat and prevent malaria, including chloroquine-resistant malaria. It contains atovaquone and proguanil. It is not recommended for severe or complicated malaria. It is taken by mouth.
Pregnancy-associated malaria (PAM) or placental malaria is a presentation of the common illness that is particularly life-threatening to both mother and developing fetus. PAM is caused primarily by infection with Plasmodium falciparum, the most dangerous of the four species of malaria-causing parasites that infect humans. During pregnancy, a woman faces a much higher risk of contracting malaria and of associated complications. Prevention and treatment of malaria are essential components of prenatal care in areas where the parasite is endemic – tropical and subtropical geographic areas. Placental malaria has also been demonstrated to occur in animal models, including in rodent and non-human primate models.
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.
Fumarranol is a drug which acts as an inhibitor of the type 2 methionine aminopeptidase enzyme METAP2. It was derived by structural modification of the natural product fumagillin. It was originally developed as an anti-angiogenesis drug for the treatment of cancer, but it was subsequently found to bind with high affinity to the METAP2 enzyme in malaria parasites and has been investigated as a potential treatment for malaria.
