Milbemycin

{{Short description|Class of chemical compounds}} The '''milbemycins''' are a group of macrolides chemically related to the avermectins and were first isolated in 1972 from ''Streptomyces hygroscopicus''. They are used in veterinary medicine as antiparasitic agents against worms, ticks and fleas.<ref name="ECSOC2">[http://ecsoc2.hcc.ru/ecsoc-2/dl001/insecticides.html The 2nd International Electronic Conference on Synthetic Organic Chemistry: Insecticides] {{webarchive|url=https://web.archive.org/web/20080418065116/http://ecsoc2.hcc.ru/ecsoc-2/dl001/insecticides.html |date=2008-04-18 }}</ref> They also show insecticida<nowiki/>l and acaricidal activity.<ref name=":02">{{Cite book |last1=Jeschke |first1=Peter |url=https://onlinelibrary.wiley.com/doi/book/10.1002/9783527699261 |title=Modern Crop Protection Compounds |last2=Witschel |first2=Matthias |last3=Krämer |first3=Wolfgang |last4=Schirmer |first4=Ulrich |date=25 January 2019 |publisher=Wiley-VCH |isbn=9783527699261 |edition=3rd |pages=1478–1500 |chapter=33.6 Glutamate-gated Chloride Channel Allosteric Modulators: Avermectins and Milbemycins |doi=10.1002/9783527699261 }}</ref>

__TOC__ == Mechanism of action == Milbemycins have a similar mechanism of action, but a longer half-life than the avermectins. They open glutamate-sensitive chloride channels in neurons and myocytes of invertebrates, leading to hyperpolarisation of these cells and blocking of signal transfer.<ref name=":02" /> They are in IRAC class 6.<ref>{{cite journal |last1=Sparks |first1=Thomas C |last2=Storer |first2=Nicholas |last3=Porter |first3=Alan |last4=Slater |first4=Russell |last5=Nauen |first5=Ralf |date=2021 |title=Insecticide resistance management and industry: the origins and evolution of the I nsecticide R esistance A ction C ommittee (IRAC) and the mode of action classification scheme |journal=Pest Management Science |volume=77 |issue=6 |pages=2609–2619 |doi=10.1002/ps.6254 |issn=1526-498X |pmc=8248193 |pmid=33421293 |bibcode=2021PMSci..77.2609S |doi-access=free}}</ref>

Milbemycin is effective against some avermectin-resistant insects.<ref name="pmid34550409"/>

== Biosynthesis == Like avermectins, milbemycins are products of fermentation by ''Streptomyces'' species. A grand total of five species, namely ''S. hygroscopicus'', ''S. griseochromogenes'', ''S. cyaneogriseus'', ''S. nanchanggensis'' and ''S. bingchenggensis'', are known to produce this family of compounds.<ref name="pmid34550409">{{cite journal |last1=Yan |first1=YS |last2=Xia |first2=HY |title=Recent advances in the research of milbemycin biosynthesis and regulation as well as strategies for strain improvement. |journal=Archives of Microbiology |date=December 2021 |volume=203 |issue=10 |pages=5849–5857 |doi=10.1007/s00203-021-02575-1 |pmid=34550409|bibcode=2021ArMic.203.5849Y |s2cid=237594779 }}</ref>

The biosynthetic cluster from ''S. bingchenggensis'' and ''S. nanchanggensis'' have been sequenced and analyzed, partly by analogy to the homologous biosynthetic cluster for avermectin. New regulatory elements that control the production of milbemycins are being identified in hopes to improve the industrial fermentation yield of milbemycins, which (as of 2021) is much lower than that of avermectin.<ref name="pmid34550409"/>

An alternative pathway to higher yields was demonstrated in 2017, when select genes from ''S. avermitilis'' were swapped out so the avermectin producer makes milbemycin instead.<ref name="pmid34550409"/>

== Examples == {{missing information|section|source species for examples ({{PMID|30689104}}, {{PMID|27604457}}), commercialized 5-oxo ({{PMID|30121749}})|date=October 2023}} frame {| class="wikitable" |- ! Name !! =R1 !! =R2 !! –R3 |- | Milbemectin || –H, (β)–OH || –H, –H || –CH3 : –CH2CH3 = 3:7 |- | Milbemycin oxime || =NOH || –H, –H || –CH3 : –CH2CH3 = 3:7 |- | Moxidectin || –H, (β)–OH || =NOCH3 || (''Z'')–C(CH3)=CH–CH(CH3)2<ref name="ECSOC2" /> |- | Nemadectin || –H, (β)–OH || –H, (α)–OH || (''Z'')–C(CH3)=CH–CH(CH3)2<ref name="ECSOC2" /> |}

== References == {{reflist}}

Category:Anthelmintics Category:Insecticides