Ivermectin B1a
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| Category | Antibiotics |
| Catalog number | BBF-04296 |
| CAS | 70161-11-4 |
| Molecular Weight | 875.12 |
| Molecular Formula | C48H74O14 |
| Purity | >95% by HPLC |
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Description
It is the major component (>80%) of the commercial anthelmintic, ivermectin. It exerts its anthelmintic effects by binding to glutamate-gated chloride channels expressed on nematode neurones and pharyngeal muscle cells. It is also a potent insecticide.
Specification
| Related CAS | 71827-03-7 |
| Synonyms | Dihydroavermectin B1a; Ivermectin; 22,23-Dihydroavermectin B1a; 5-O-Demethyl-22,23-dihydro-avermectin A1a; Ivermectin Impurity I |
| Storage | Store at -20°C under inert atmosphere |
| IUPAC Name | (1R,4S,5'S,6R,6'R,8R,10E,12S,13S,14E,16E,20R,21R,24S)-6'-[(2S)-butan-2-yl]-21,24-dihydroxy-12-[(2R,4S,5S,6S)-5-[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-4-methoxy-6-methyloxan-2-yl]oxy-5',11,13,22-tetramethylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2'-oxane]-2-one |
| Canonical SMILES | CCC(C)C1C(CCC2(O1)CC3CC(O2)CC=C(C(C(C=CC=C4COC5C4(C(C=C(C5O)C)C(=O)O3)O)C)OC6CC(C(C(O6)C)OC7CC(C(C(O7)C)O)OC)OC)C)C |
| InChI | InChI=1S/C48H74O14/c1-11-25(2)43-28(5)17-18-47(62-43)23-34-20-33(61-47)16-15-27(4)42(26(3)13-12-14-32-24-55-45-40(49)29(6)19-35(46(51)58-34)48(32,45)52)59-39-22-37(54-10)44(31(8)57-39)60-38-21-36(53-9)41(50)30(7)56-38/h12-15,19,25-26,28,30-31,33-45,49-50,52H,11,16-18,20-24H2,1-10H3/b13-12+,27-15+,32-14+/t25-,26-,28-,30-,31-,33+,34-,35-,36-,37-,38-,39-,40+,41-,42-,43+,44-,45+,47+,48+/m0/s1 |
| InChI Key | AZSNMRSAGSSBNP-XPNPUAGNSA-N |
| Source | Semi-synthetic |
Properties
| Appearance | White Solid |
| Antibiotic Activity Spectrum | Parasites |
| Boiling Point | 940.4±65.0°C at 760 mmHg |
| Melting Point | 161-165°C |
| Density | 1.2±0.1 g/cm3 |
| Solubility | Slightly soluble in Chloroform, DMSO |
Reference Reading
1. Possible anxiolytic effects of ivermectin in rats
S R A N Stilck, M M Bernardi, H de Souza Spinosa Vet Res Commun . 2002 Jun;26(4):309-21. doi: 10.1023/a:1016094726033.
Ivermectin, a mixture of 22,23-dihydroavermectin B1a (> or = 80%) and B1b (< or =20%), is produced by Streptomyces avermectilis, an actinomycete. It is a macrocyclic lactone disaccharide, a member of the avermectin family, and is used as an antiparasitic drug. Previous studies performed in our laboratory showed that doramectin, another avermectin drug, interferes with GABAergic-related behaviours, leading to anxiety and seizures. The objective of the present study was to examine the effects of ivermectin (0.5 and 1.0 mg/kg) on the central nervous system of rats, using behavioural models related to GABAergic neurotransmission. A known anxiolytic drug, diazepam, was used as a positive control. Open field and elevated plus-maze behaviours, as well as conflict behaviour to a conditioned response, were assessed. The effects of ivermectin and diazepam in reversing the anxiety induced by picrotoxin was studied. The protective effects of ivermectin on pentylenetetrazole- and picrotoxin-induced seizures were also investigated. In the open field, 1.0 mg/kg ivermectin decreased locomotion frequency at 15 and 60 min of observation, rearing behaviour showed a biphasic effect at 15 and 30 min and duration of immobility was increased in all sessions after 1.0 mg/kg ivermectin. These data suggest anxiolytic or sedative effects. Ivermectin and diazepam both had a tendency to cause an increase both in the number of entries into the open arms and on the time spent in the open arms of an elevated plus-maze. Picrotoxin on its own reduced the number of entries as well as the time spent in the open arms. Both diazepam and ivermectin reversed these effects of picrotoxin. In conflict behaviour analysis, ivermectin and diazepam gave the classic effect of an anxiolytic drug, reversing the conditioned response to shock. Ivermectin protected rats from the convulsant effects of pentylenetetrazole but not from those of picrotoxin. Thus, ivermectin had the pharmacological profile of an anxiolytic drug with GABAergic properties. The lack of effect on seizures induced by picrotoxin suggests that the action of ivermectin is different from that of the benzodiazepine drugs.
2. Ivermectin efficacy against Biomphalaria, intermediate host snail vectors of Schistosomiasis
Koh Suzuki, Ana Rosa Linde-Arias, Takeshi Yamada, Paulo Marcos Zech Coelho, Naftale Katz, Toshiaki Sunazuka, Neusa Araújo, Yuki Horimatsu, Carlos Medicis Morel, Satoshi Ōmura J Antibiot (Tokyo) . 2017 May;70(5):680-684. doi: 10.1038/ja.2017.31.
The impact of ivermectin on adult snails of the genus Biomphalaria (B. glabrata, B. tenagophila and B. straminea), B. glabrata infected with Schistosoma mansoni, snail egg-masses cercariae and miracidia, as well as on guppy fish (Poecilia reticulata) was examined and evaluated. Biomphalaria snails, egg-masses, parasite stages and guppies were all exposed to different concentrations of ivermectin for 24 h, followed by regular observations of mortality. The calculated lethal doses of ivermectin were around an LD50of 0.03 μg ml-1, and an LD90of 0.3 μg ml-1for the three species of snails. Specimens of B. glabrata actually shedding parasite cercariae all died when exposed to ivermectin at a concentration of a mere 0.01 μg ml-1. Ivermectin B1a, the major (80%) component of commercially available ivermectin, proved to be inactive, and it was the minor (20%) component, ivermectin B1b, which caused snail death. Snail egg-masses were not affected, even at the highest concentration of 100 μg ml-1. With respect to S. mansoni parasite stages, 0.2 μg ml-1ivermectin killed 50% of cercariae and miracidia within five minutes, rising to 90% after 30 min. Mortality of guppy fish within 24 h of exposure to ivermectin at concentrations of 0.5 μg ml-1and 0.01 μg ml-1, were 100% and 30%, respectively. The concentration of 0.01 μg ml-1that killed Schistosoma mansoni-infected snails only caused 30% mortality in guppy fish. Ivermectin can be considered a promising molluscicide, especially as it is more potent against infected snails than uninfected ones, although it has no impact on egg-masses. Ivermectin and its derivatives could be explored in the search for a new agent to help control schistosomiasis transmission.
3. Avermectin B1a production in Streptomyces avermitilis is enhanced by engineering aveC and precursor supply genes
Yanting You, Ying Wen, Gang Liu, Yi Hao, Zhi Chen, Jilun Li Appl Microbiol Biotechnol . 2022 Mar;106(5-6):2191-2205. doi: 10.1007/s00253-022-11854-w.
Avermectins (AVEs) are economically potent anthelmintic agents produced by Streptomyces avermitilis. Among eight AVE components, B1a exhibits the highest insecticidal activity. The purpose of this study was to enhance B1a production, particularly in the high-yielding industrial strain A229, by a combination strategy involving the following steps. (i) aveC gene was engineered to increase B1a:B2a ratio. Three aveC variants (aveC2m, aveC5m, and aveC8m, respectively encoding two, five, and eight amino acid mutations) were synthesized by fusion PCR. B1a:B2a ratio in A229 derivative having kasOp*-controlled aveC8m reached 1.33 (B1a and B2a titers were 8120 and 6124 μg/mL). Corresponding values in A229 were 0.99 and 6447 and 6480 μg/mL. (ii) β-oxidation pathway genes fadD and fadAB were overexpressed in wild-type (WT) strain and A229 to increase supply of acyl-CoA precursors for AVE production. The resulting strains all showed increased B1a titer. Co-overexpression of pkn5p-driven fadD and fadAB in A229 led to B1a titer of 8537 μg/mL. (iii) Genes bicA and ecaA involved in cyanobacterial CO2-concentrating mechanism (CCM) were introduced into WT and A229 to enhance carboxylation velocity of acetyl-CoA and propionyl-CoA carboxylases, leading to increased supply of malonyl- and methylmalonyl-CoA precursors and increased B1a titer. Co-expression of bicA and ecaA in A229 led to B1a titer of 8083 μg/mL. (iv) aveC8m, fadD-fadAB, and bicA-ecaA were co-overexpressed in A229, resulting in maximal B1a titer (9613 μg/mL; 49.1% increase relative to A229). Our findings demonstrate that the combination strategy we provided here is an efficient approach for improving B1a production in industrial strains.Key points· aveC mutation increased avermectin B1a:B2a ratio and B1a titer.· Higher levels of acyl-CoA precursors contributed to enhanced B1a production.· B1a titer in an industrial strain was increased by 49.1% via a combination strategy.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
