| Record Information |
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| Version | 2.0 |
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| Creation Date | 2009-06-08 17:06:10 UTC |
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| Update Date | 2014-12-24 20:22:52 UTC |
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| Accession Number | T3D0831 |
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| Identification |
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| Common Name | Isoimperatorin |
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| Class | Small Molecule |
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| Description | Isoimperatorin is a tumor necrosis factor antagonist isolated from Glehniae root or from Poncirus trifoliate Raf (4). Furocoumarins, are phototoxic and photocarcinogenic. They intercalate DNA and photochemically induce mutations. Furocoumarins are botanical phytoalexins found to varying extents in a variety of vegetables and fruits, notably citrus fruits. The levels of furocoumarins present in our diets, while normally well below that causing evident acute phototoxicity, do cause pharmacologically relevant drug interactions. Some are particularly active against cytochrome P450s. For example, in humans, bergamottin and dihydroxybergamottin are responsible for the 'grapefruit juice effect', in which these furanocoumarins affect the metabolism of certain drugs. |
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| Compound Type | - Aromatic Hydrocarbon
- Ester
- Ether
- Food Toxin
- Furocoumarin
- Natural Compound
- Organic Compound
- Plant Toxin
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| Chemical Structure | |
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| Synonyms | | Synonym | | 4-[(3-Methyl-2-butenyl)oxy]-7H-furo[3,2-g]chromen-7-one | | 7,4-[(3-Methyl-2-butenyl)oxy]-7H-furo[3,2-g]-1-benzopyran-7-one | | Iso-imperatorin |
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| Chemical Formula | C16H14O4 |
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| Average Molecular Mass | 270.280 g/mol |
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| Monoisotopic Mass | 270.089 g/mol |
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| CAS Registry Number | 482-45-1 |
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| IUPAC Name | 4-[(3-methylbut-2-en-1-yl)oxy]-7H-furo[3,2-g]chromen-7-one |
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| Traditional Name | 4-[(3-methylbut-2-en-1-yl)oxy]furo[3,2-g]chromen-7-one |
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| SMILES | CC(C)=CCOC1=C2C=CC(=O)OC2=CC2=C1C=CO2 |
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| InChI Identifier | InChI=1S/C16H14O4/c1-10(2)5-7-19-16-11-3-4-15(17)20-14(11)9-13-12(16)6-8-18-13/h3-6,8-9H,7H2,1-2H3 |
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| InChI Key | InChIKey=IGWDEVSBEKYORK-UHFFFAOYSA-N |
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| Chemical Taxonomy |
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| Description | belongs to the class of organic compounds known as psoralens. These are organic compounds containing a psoralen moiety, which consists of a furan fused to a chromenone to for 7H-furo[3,2-g]chromen-7-one. |
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| Kingdom | Organic compounds |
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| Super Class | Phenylpropanoids and polyketides |
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| Class | Coumarins and derivatives |
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| Sub Class | Furanocoumarins |
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| Direct Parent | Psoralens |
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| Alternative Parents | |
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| Substituents | - Psoralen
- Benzopyran
- 1-benzopyran
- Benzofuran
- Alkyl aryl ether
- Pyranone
- Benzenoid
- Pyran
- Heteroaromatic compound
- Furan
- Lactone
- Ether
- Oxacycle
- Organoheterocyclic compound
- Organic oxygen compound
- Hydrocarbon derivative
- Organic oxide
- Organooxygen compound
- Aromatic heteropolycyclic compound
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| Molecular Framework | Aromatic heteropolycyclic compounds |
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| External Descriptors | |
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| Biological Properties |
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| Status | Detected and Not Quantified |
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| Origin | Exogenous |
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| Cellular Locations | |
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| Biofluid Locations | Not Available |
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| Tissue Locations | Not Available |
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| Pathways | Not Available |
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| Applications | Not Available |
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| Biological Roles | |
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| Chemical Roles | |
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| Physical Properties |
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| State | Solid |
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| Appearance | White powder. |
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| Experimental Properties | | Property | Value |
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| Melting Point | Not Available | | Boiling Point | Not Available | | Solubility | Not Available | | LogP | Not Available |
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| Predicted Properties | |
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| Spectra |
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| Spectra | | Spectrum Type | Description | Splash Key | Deposition Date | View |
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| Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | splash10-0596-5390000000-1bf0c24c340b994423c5 | 2021-09-23 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | Not Available | 2021-10-12 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 20V, Positive | splash10-0udi-0290000000-6fc9699eb703287cc20c | 2021-09-20 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 10V, Positive | splash10-0udi-0090000000-91b67568346d3505ed84 | 2021-09-20 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 40V, Positive | splash10-0005-5900000000-456019d3d6f24671b66c | 2021-09-20 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 10V, Negative | splash10-014i-0090000000-b0c02d050a925e7d5577 | 2021-09-20 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 20V, Negative | splash10-014i-3590000000-9f0a858c5257f0f68341 | 2021-09-20 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 40V, Negative | splash10-0wos-5960000000-45ec8597e6a51c9b31ac | 2021-09-20 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-00di-1090000000-8ac6c0a5fb70291a1eaa | 2016-08-02 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-014i-9080000000-6df3f42b8b7e78aa7f2d | 2016-08-02 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-0gb9-9530000000-fb7bbc5a1973fd1a795d | 2016-08-02 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-014i-0090000000-300965788bf7c4527eb0 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-0udi-0290000000-9161a37ce9657cf9058e | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-0a4i-0910000000-ff19b981b89111d7fcb8 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-0udi-0090000000-2e5a86e101fa40f235c9 | 2021-10-12 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-0udi-0090000000-2e5a86e101fa40f235c9 | 2021-10-12 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-0fb9-1940000000-e7dafddba6e1b2584175 | 2021-10-12 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-014i-0090000000-d3eedc6d74870144d16f | 2021-10-12 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-0udi-0190000000-55d1bfdb46af46eb4117 | 2021-10-12 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-0pb9-2930000000-85deed983716c2656d62 | 2021-10-12 | View Spectrum | | MS | Mass Spectrum (Electron Ionization) | splash10-0uxr-8290000000-27260c39496d6e0b6251 | 2014-09-20 | View Spectrum |
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| Toxicity Profile |
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| Route of Exposure | Not Available |
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| Mechanism of Toxicity | Isoimperatorin is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen. The mechanism of action many furocoumarins is based on their ability to form photoadducts with DNA and other cellular components such as RNA, proteins, and several proteins found in the membrane such as phospholipases A2 and C, Ca-dependent and cAMPdependent protein-kinase and epidermal growth factor. Furocoumarins intercalate between base pairs of DNA and after ultraviolet-A irradiation, giving cycloadducts. (4). |
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| Metabolism | Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of OP exposure. |
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| Toxicity Values | Not Available |
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| Lethal Dose | Not Available |
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| Carcinogenicity (IARC Classification) | Not listed by IARC. IARC has assessed other furocoumarins, classifying 8-methoxypsoralen as carcinogenic to humans (Group 1), 5-methoxypsoralen as possibly carcinogenic to humans (Group 2A), and certain other furocoumarins as not being classifiable as to their carcinogenicity to humans (Group 3). (5) |
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| Uses/Sources | Not Available |
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| Minimum Risk Level | Not Available |
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| Health Effects | Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides. The furocoumarin 8-methoxypsoralen is carcinogenic to humans, and possibly 5-methoxypsoralen as well (5). There is some evidence from mouse studies that other furocoumarins are carcinogenic when combined with exposure to UVA radiation (1). The SKLM regards the additional risk of skin cancer arising from the consumption of typical quantities of furocoumarin-containing foods, which remain significantly below the range of phototoxic doses, as insignificant. However, the consumption of phototoxic quantities cannot be ruled out for certain foods, particularly celery and parsnips, that may lead to significant increases in furocoumarin concentrations, depending on the storage, processing and production conditions. (6) Furocoumarin photochemotherapy is known to induce a number of side-effects including erythema, edema, hyperpigmentation, and premature aging of skin. All photobiological effects of furocoumarins result from their photochemical reactions. Because many dietary or water soluble furocoumarins are strong inhibitors of cytochrome P450s, they will also cause adverse drug reactions when taken with other drugs. Limited evidence of carcinogenic effect. (4) |
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| Symptoms | Symptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result. |
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| Treatment | If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally. |
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| Normal Concentrations |
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| Not Available |
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| Abnormal Concentrations |
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| Not Available |
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| External Links |
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| DrugBank ID | Not Available |
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| HMDB ID | Not Available |
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| PubChem Compound ID | 68081 |
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| ChEMBL ID | CHEMBL448060 |
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| ChemSpider ID | 61393 |
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| KEGG ID | C16976 |
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| UniProt ID | Not Available |
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| OMIM ID | |
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| ChEBI ID | 66071 |
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| BioCyc ID | PHYTOALEXIN-CMPD |
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| CTD ID | C055542 |
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| Stitch ID | Isoimperatorin |
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| PDB ID | Not Available |
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| ACToR ID | Not Available |
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| Wikipedia Link | Not Available |
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| References |
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| Synthesis Reference | Not Available |
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| MSDS | T3D0831.pdf |
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| General References | - Mullen MP, Pathak MA, West JD, Harrist TJ, Dall'Acqua F: Carcinogenic effects of monofunctional and bifunctional furocoumarins. Natl Cancer Inst Monogr. 1984 Dec;66:205-10. [6531030 ]
- Ostertag E, Becker T, Ammon J, Bauer-Aymanns H, Schrenk D: Effects of storage conditions on furocoumarin levels in intact, chopped, or homogenized parsnips. J Agric Food Chem. 2002 Apr 24;50(9):2565-70. [11958623 ]
- Santana L, Uriarte E, Roleira F, Milhazes N, Borges F: Furocoumarins in medicinal chemistry. Synthesis, natural occurrence and biological activity. Curr Med Chem. 2004 Dec;11(24):3239-61. [15579011 ]
- Herboreal Ltd - Manufacturer of rare phytochemicals (2009). [Link]
- International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
- DFG Senate Commission on Food Safety (SKLM): Toxicological Assessment of Furocoumarins in Foodstuffs (2006) [Link]
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| Gene Regulation |
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| Up-Regulated Genes | | Gene | Gene Symbol | Gene ID | Interaction | Chromosome | Details |
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| Down-Regulated Genes | Not Available |
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