Ivermectin B1 aglycone
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| Category | Enzyme inhibitors |
| Catalog number | BBF-04574 |
| CAS | 123997-59-1 |
| Molecular Weight | 586.76 |
| Molecular Formula | C34H50O8 |
| Purity | >99% by HPLC |
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Description
A semi-synthetic product produced by hydrolysing the disaccharide unit of ivermectin. It is a potent inhibitor of nematode larval development, but is devoid of paralytic activity. The aglycone is used as a sensitive probe for the detection of some types of ivermectin resistance. An impurity of Ivermectin.
Specification
| Synonyms | Dihydroavermectin B1 aglycone; (6R,13S,25R)-5-O-Demethyl-28-deoxy-6,28-epoxy-13-hydroxy-25-[(1S)-1-methylpropyl]-milbemycin B; [6R,13S,25R(S)]-5-O-Demethyl-28-deoxy-6,28-epoxy-13-hydroxy-25-(1-methylpropyl)-milbemycin B; 22,23-Dihydroavermectin B1a Aglycon; Ivermectin Aglycone; 13-O-De[4-O-(2,6-dideoxy-3-O-methyl-α-L-glucopyranosyl)-2,6-dideoxy-3-O-methyl-α-L-glucopyranosyl]-22,23-dihydro-27-noravermectin A1 |
| Storage | Store at −86°C under inert atmosphere |
| IUPAC Name | (1R,4S,5'S,6R,6'R,8R,10E,12S,13S,14E,16E,20R,21R)-6'-[(2S)-butan-2-yl]-12,21,24-trihydroxy-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)O)C)C |
| InChI | InChI=1S/C34H50O8/c1-7-19(2)30-22(5)13-14-33(42-30)17-26-16-25(41-33)12-11-21(4)28(35)20(3)9-8-10-24-18-39-31-29(36)23(6)15-27(32(37)40-26)34(24,31)38/h8-11,15,19-20,22,25-31,35-36,38H,7,12-14,16-18H2,1-6H3/b9-8+,21-11+,24-10+/t19-,20-,22-,25+,26-,27-,28-,29+,30+,31+,33+,34?/m0/s1 |
| InChI Key | XOCXXEYUGYTCNG-CKHQCAAISA-N |
| Source | Semi-synthetic |
Properties
| Appearance | White Solid |
| Antibiotic Activity Spectrum | Parasites |
| Boiling Point | 776.2±60.0°C at 760 mmHg |
| Melting Point | 149-154°C |
| Density | 1.2±0.1 g/cm3 |
| Solubility | Soluble in Ethanol, Methanol, DMF, DMSO, Chloroform; Poorly soluble in Water |
Reference Reading
1. Solubilization and characterization of a high affinity ivermectin binding site from Caenorhabditis elegans
D F Cully, P S Paress Mol Pharmacol . 1991 Aug;40(2):326-32.
Ivermectin is a member of the avermectin family of compounds that are used to treat helminth and arthropod diseases in humans, domestic animals, and plants. A membrane-bound high affinity ivermectin binding site was extracted from Caenorhabditis elegans with the nonionic detergent 1-O-n-octyl-beta-D-glucopyranoside. The free-living nematode C. elegans is highly sensitive to the avermectins and was used as a model of parasitic nematodes. The membrane-bound and detergent-solubilized ivermectin binding sites are stable and exhibit high affinity binding, with dissociation constants of 0.11 nM and 0.20 nM, respectively. The maximum binding of [3H]ivermectin is 0.54 pmol/mg of membrane protein and 0.66 pmol/mg of detergent-soluble protein. Kinetic analysis of ivermectin binding shows that the ivermectin binding sites form a slowly reversible complex with ivermectin. The rates of dissociation of [3H]ivermectin with the solubilized and membrane-bound binding sites are 0.005 min-1 and 0.006 min-1, respectively. The association rate of the soluble binding site is 0.053 nM-1 min-1, slightly slower than that observed for the membrane-bound site, 0.074 nM-1 min-1. To characterize the ivermectin binding site, competition experiments were performed by inhibiting [3H]ivermectin binding with several avermectin derivatives and the neurotransmitter gamma-aminobutyric acid (GABA). The order of potency was 22,23-dihydroavermectin B1a monosaccharide greater than 22,23-dihydroavermectin B1a aglycone greater than 3,4,8,9,10,11,22,23-octahydro B1 avermectin for both the membrane-bound and NOG-soluble binding sites. GABA did not compete with ivermectin binding, although it has been suggested that ivermectin acts at the GABA-gated chloride channel in some invertebrate systems. Optimum ivermectin binding and assay conditions have been determined. The detergent-soluble ivermectin binding site appears to be negatively charged and has a pl of 4.0 and an apparent Mr in Triton X-100 micelles of 340,000. Detergent solubilization of a high affinity ivermectin binding site will enable the subsequent purification and characterization of a putative site of ivermectin action.
2. Identification of cytochrome P4503A as the major enzyme sub-family responsible for the metabolism of 22,23-dihydro-13-O-[(2-methoxyethoxy)methyl]-avermectin B1 aglycone by rat liver microsomes
B A Halley, Z Zeng, N W Andrew Xenobiotica . 1997 Oct;27(10):985-94. doi: 10.1080/004982597239967.
1. Metabolism of 22,23-dihydro-13-O-[(2-methoxyethoxy)methyl]-avermectin B1 aglycone (MEM-H2B1), a new avermectin, by rat liver microsomes has been studied. Metabolites identified were formed by demethylation of the methoxyethoxymethoxy (MEM) side chain, loss of the MEM side chain, partial cleavage and further oxidation of the MEM side chain, and oxidation of the aglycone after cleavage of the MEM side chain. 2. The specific cytochrome P450 isoforms involved in the metabolism of MEM-H2B1 were identified through immunoinhibition studies. Among several antibodies prepared against various cytochrome P450s, only anti-rat P4503A IgG inhibited MEM-H2B1 metabolism by liver microsomes from the untreated rat. Moreover, troleandomycin, a selective suicide inhibitor for enzymes of the cytochrome P4503A family, inhibited the total metabolism by > 80%. These results clearly indicate that cytochrome P4503A is primarily responsible for the metabolism of MEM-H2B1. 3. Secondary metabolism was evident in the metabolism of MEM-H2B1 by dexamethasone and phenobarbital induced liver microsomes, where different isoform(s) of cytochrome P4503A could be involved in these multiple step reactions.
3. Avermectins and milbemycins against Fasciola hepatica: in vivo drug efficacy and in vitro receptor binding
D A Ostlind, W L Shoop, S P Rohrer, H W Haines, B F Michael, M H Fisher, H Mrozik, G Mickle Int J Parasitol . 1995 Aug;25(8):923-7. doi: 10.1016/0020-7519(95)00026-x.
Few studies have examined activity against trematodes for the avermectin/milbemycin class of anthelmintics. To gain insight into this, 12 different members of the avermectin/milbemycin mode of action class were tested against juvenile Fasciola hepatica in a mouse model. The compounds chosen were Avermectin A1, Avermectin A2, Avermectin B1, Avermectin B2, Ivermectin, Ivermectin monosaccharide, Ivermectin aglycone, 13-deoxy ivermectin aglycone, Moxidectin, 13-O-methoxyethoxymethyl ivermectin aglycone, 4"-deoxy-4"-epi-methylamino avermectin B1, and 4"-deoxy-4"-epi-acetylamino avermectin B1 5-oxime. Each of these compounds was administered orally to 4 mice at 2.0 mg kg-1. These mice had been administered 3 metacercariae of F. hepatica 14 days prior to treatment and all mice were necropsied 4 days after treatment. At necropsy, none of the individual avermectin or milbemycin-treated groups showed any significant activity (P > 0.05) against juvenile F. hepatica relative to a vehicle-treated control. In a receptor binding study, adult F. hepatica that had been obtained from sheep were homogenized, their membranes incubated in the presence of 3H-ivermectin, and then measured for high affinity binding sites. The same was done with the free-living nematode, Caenorhabditis elegans. While the C. elegans membranes displayed high affinity 3H-ivermectin binding sites over the range of ivermectin concentrations tested (5-100 nM), no significant 3H-ivermectin binding sites were detected in the F. hepatica membranes. Based on these data, it seems unlikely that any avermectin or milbemycin will show activity against F. hepatica, and certainly makes one pessimistic about possible activity of this mode of action class against trematodes in general.
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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 ╳
