Avermectin
This article is missing information about what the chemical structures of
A1, A2, B1, B2 each are. The Abamectin pic can be reused, just need one more R group according to YoongKim04.(September 2023) |
The avermectins are a series of
Half of the 2015 Nobel Prize in Physiology or Medicine was awarded to William C. Campbell and Satoshi Ōmura for discovering avermectin,[4] "the derivatives of which have radically lowered the incidence of river blindness and lymphatic filariasis, as well as showing efficacy against an expanding number of other parasitic diseases."
History
In 1978, an actinomycete was isolated at the
In 2002, Yoko Takahashi and others at the Kitasato Institute for Life Sciences, Kitasato University, and at the Kitasato Institute, proposed that Streptomyces avermitilis be renamed Streptomyces avermectinius.[6]
Dosing
A commonly used therapy in recent times has been based on oral,
Mechanism of action
The avermectins block the transmission of electrical activity in invertebrate nerve and muscle cells mostly by enhancing the effects of
Toxicity and side effects
Avermectin biosynthesis
The gene cluster for biosynthesis of avermectin from
The avermectin initial aglycon is synthesized by the polyketide synthase activity of four proteins (AVES 1, AVES 2, AVES 3, and AVES 4). The activity of this enzyme complex is similar to type I polyketide synthases.[1] Either 2-methylbutyryl CoA or isobutyryl CoA can be used as starting units and are extended by seven acetate units and five propionate units to produce avermectin “a” series or “b” series, respectively.[1] The initial aglycon is subsequently released from the thioesterase domain of AVES 4 by formation of an intramolecular cyclic ester.[1]
The avermectin initial aglycon is further modified by other enzymes in the avermectin biosynthetic gene cluster. AveE has cytochrome P450 monooxygenase activity and facilitates the furan ring formation between C6 and C8.[1] AveF has NAD(P)H-dependent ketoreductase activity which reduces the C5 keto group to a hydroxyl.[1] AveC influences the dehydratase activity in module two (affecting C22-C23), although the mechanism by which it does this is not clear.[20][1] AveD has SAM-dependent C5 O-methyltransferase activity.[1] Whether AveC or AveD acts on the aglycon determines whether the resulting avermectin aglycon will produce avermectin, series “A” or “B” and series 1 or 2 (see synthesis schematic diagram table), respectively.[1]
Nine open reading frames (orf1 and aveBI-BVIII) are downstream of aveA4, which are known involved with glycosylation and sugar synthesis.[1] AveBII-BVIII are responsible for synthesis of dTDP-L-oleandrose and AveBI is responsible for glycosylation of the avermectin aglycon with the dTDP-sugar.[1] The sequence of orf1 suggests that its product will have reductase activity, but this functionality does not appear to be necessary for avermectin synthesis.[1]
Other uses
Abamectin is the active ingredient in some commercial ant bait traps. Ivermectin, formulated from Avermectin, has a wide variety of uses in human beings. According to a paper (Ivermectin: “Wonder Drug” from Japan: the human use perspective) written by the drugs co-creator Satoshi Ōmura and Andy Crump for The Japan Academy, Ivermectin has improved the lives of billions of people worldwide and not solely for uses as an anti parasitic.[21]
See also
- Milbemycins are a chemically closely related group of parasiticides.
- Avermectin/ivermectin glycorandomization
References
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- ^ "The Nobel Prize in Physiology or Medicine 2015". Nobel Prize. 2020-12-03. Retrieved 2020-12-03.
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- ^ Peter, John. "Ivermectin".
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