FRCD

Common Name	Isoimperatorin(F03910)
2D Structure
Description	Isoimperatorin is a tumor necrosis factor antagonist isolated from Glehniae root or from Poncirus trifoliate Raf (L579). 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.
FRCD ID	F03910
CAS Number	482-45-1
PubChem CID	68081
Formula	C16H14O4
IUPAC Name	4-(3-methylbut-2-enoxy)furo[3,2-g]chromen-7-one
InChI Key	IGWDEVSBEKYORK-UHFFFAOYSA-N
InChI	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
Canonical SMILES	CC(=CCOC1=C2C=CC(=O)OC2=CC3=C1C=CO3)C
Isomeric SMILES	CC(=CCOC1=C2C=CC(=O)OC2=CC3=C1C=CO3)C
Synonyms	4-[(3-methylbut-2-en-1-yl)oxy]-7h-furo[3,2-g]chromen-7-one Isoimperatorin 482-45-1 Iso Imperatorin 4-(3-methylbut-2-enoxy)furo[3,2-g]chromen-7-one UNII-0ZMV066080 CHEMBL448060 CHEBI:66071 0ZMV066080 Iso-imperatorin
Classifies	Plant Toxin
Update Date	Nov 13, 2018 17:07

Kingdom	Organic compounds
Superclass	Phenylpropanoids and polyketides
Class	Coumarins and derivatives
Subclass	Furanocoumarins
Intermediate Tree Nodes	Linear furanocoumarins
Direct Parent	Psoralens
Alternative Parents	Hydrocarbon derivatives Organic oxides Alkyl aryl ethers Oxacyclic compounds Furans Heteroaromatic compounds Benzenoids 1-benzopyrans Lactones Pyranones and derivatives Benzofurans
Molecular Framework	Aromatic heteropolycyclic compounds
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
Description	This compound 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.

Property Name	Property Value
Molecular Weight	270.284
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Complexity	436
Monoisotopic Mass	270.089
Exact Mass	270.089
XLogP	3.8
Formal Charge	0
Heavy Atom Count	20
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Isotope Atom Count	0
Covalently-Bonded Unit Count	1

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB+	0.8369
Human Intestinal Absorption	HIA+	0.9968
Caco-2 Permeability	Caco2+	0.5576
P-glycoprotein Substrate	Substrate	0.6532
P-glycoprotein Inhibitor	Inhibitor	0.7971
P-glycoprotein Inhibitor	Inhibitor	0.5926
Renal Organic Cation Transporter	Non-inhibitor	0.7189
Distribution
Subcellular localization	Mitochondria	0.7705
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.8277
CYP450 2D6 Substrate	Non-substrate	0.8863
CYP450 3A4 Substrate	Substrate	0.5527
CYP450 1A2 Inhibitor	Inhibitor	0.9055
CYP450 2C9 Inhibitor	Inhibitor	0.8278
CYP450 2D6 Inhibitor	Inhibitor	0.7167
CYP450 2C19 Inhibitor	Inhibitor	0.9153
CYP450 3A4 Inhibitor	Inhibitor	0.7687
CYP Inhibitory Promiscuity	High CYP Inhibitory Promiscuity	0.9416
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9070
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.9034
AMES Toxicity	AMES toxic	0.9226
Carcinogens	Non-carcinogens	0.9347
Fish Toxicity	High FHMT	0.9954
Tetrahymena Pyriformis Toxicity	High TPT	0.9928
Honey Bee Toxicity	High HBT	0.9007
Biodegradation	Not ready biodegradable	0.6754
Acute Oral Toxicity	III	0.6372
Carcinogenicity (Three-class)	Non-required	0.5953

Model	Value	Unit
Absorption
Aqueous solubility	-4.2678	LogS
Caco-2 Permeability	0.8806	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	2.8085	LD50, mol/kg
Fish Toxicity	-1.7032	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	0.7864	pIGC50, ug/L

Title	Journal	Date	Pubmed ID
Larvicidal activity of Cnidium monnieri fruit coumarins and structurally related compounds against insecticide-susceptible and insecticide-resistant Culex pipiens pallens and Aedes aegypti.	Pest Manag Sci	2012 Jul	22389164

Targets

General Function:: Serine hydrolase activity
Specific Function:: Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:: ACHE
Uniprot ID:: P22303
Molecular Weight:: 67795.525 Da

Kang SY, Lee KY, Sung SH, Park MJ, Kim YC: Coumarins isolated from Angelica gigas inhibit acetylcholinesterase: structure-activity relationships. J Nat Prod. 2001 May;64(5):683-5. [11374978 ]

General Function:: Steroid hydroxylase activity
Specific Function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:: CYP2C9
Uniprot ID:: P11712
Molecular Weight:: 55627.365 Da

Girennavar B, Jayaprakasha GK, Patil BS: Potent inhibition of human cytochrome P450 3A4, 2D6, and 2C9 isoenzymes by grapefruit juice and its furocoumarins. J Food Sci. 2007 Oct;72(8):C417-21. [17995595 ]

General Function:: Vitamin d3 25-hydroxylase activity
Specific Function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:: CYP3A4
Uniprot ID:: P08684
Molecular Weight:: 57342.67 Da

Girennavar B, Jayaprakasha GK, Patil BS: Potent inhibition of human cytochrome P450 3A4, 2D6, and 2C9 isoenzymes by grapefruit juice and its furocoumarins. J Food Sci. 2007 Oct;72(8):C417-21. [17995595 ]