FRCD

Common Name	Pimpinellin(F03908)
2D Structure
Description	Pimpinellin is a furocoumarin. 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	F03908
CAS Number	131-12-4
PubChem CID	4825
Formula	C13H10O5
IUPAC Name	5,6-dimethoxyfuro[2,3-h]chromen-2-one
InChI Key	BQPRWZCEKZLBHL-UHFFFAOYSA-N
InChI	InChI=1S/C13H10O5/c1-15-11-7-3-4-9(14)18-10(7)8-5-6-17-12(8)13(11)16-2/h3-6H,1-2H3
Canonical SMILES	COC1=C(C2=C(C=CO2)C3=C1C=CC(=O)O3)OC
Isomeric SMILES	COC1=C(C2=C(C=CO2)C3=C1C=CC(=O)O3)OC
Synonyms	pimpinellin 131-12-4 5,6-Dimethoxy-2H-furo[2,3-H]chromen-2-one Pimpinecilin CCRIS 4344 5,6-dimethoxyfuro[2,3-h]chromen-2-one UNII-D419UK1B4L CHEBI:8213 D419UK1B4L 2H-Furo(2,3-h)-1-benzopyran-2-one, 5,6-dimethoxy-
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	Not available
Direct Parent	Angular furanocoumarins
Alternative Parents	Hydrocarbon derivatives Organic oxides Alkyl aryl ethers Oxacyclic compounds Anisoles Furans Heteroaromatic compounds 1-benzopyrans Lactones Pyranones and derivatives Benzofurans
Molecular Framework	Aromatic heteropolycyclic compounds
Substituents	Angular furanocoumarin - Benzopyran - 1-benzopyran - Benzofuran - Anisole - Alkyl aryl ether - Pyranone - Pyran - Benzenoid - Furan - Heteroaromatic compound - Lactone - Oxacycle - Ether - Organoheterocyclic compound - Organic oxygen compound - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Aromatic heteropolycyclic compound
Description	This compound belongs to the class of organic compounds known as angular furanocoumarins. These are furanocoumarins, with a structure characterized by a furan ring angularly fused to a coumarin.

Property Name	Property Value
Molecular Weight	246.218
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	2
Complexity	366
Monoisotopic Mass	246.053
Exact Mass	246.053
XLogP	2.3
Formal Charge	0
Heavy Atom Count	18
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+	0.9073
Human Intestinal Absorption	HIA+	0.9886
Caco-2 Permeability	Caco2+	0.7454
P-glycoprotein Substrate	Non-substrate	0.5472
P-glycoprotein Inhibitor	Inhibitor	0.6382
P-glycoprotein Inhibitor	Inhibitor	0.5097
Renal Organic Cation Transporter	Non-inhibitor	0.8445
Distribution
Subcellular localization	Mitochondria	0.6582
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.8128
CYP450 2D6 Substrate	Non-substrate	0.8969
CYP450 3A4 Substrate	Non-substrate	0.5638
CYP450 1A2 Inhibitor	Inhibitor	0.9499
CYP450 2C9 Inhibitor	Non-inhibitor	0.6599
CYP450 2D6 Inhibitor	Inhibitor	0.5728
CYP450 2C19 Inhibitor	Inhibitor	0.9452
CYP450 3A4 Inhibitor	Inhibitor	0.7206
CYP Inhibitory Promiscuity	High CYP Inhibitory Promiscuity	0.8133
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9682
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.9503
AMES Toxicity	Non AMES toxic	0.5874
Carcinogens	Non-carcinogens	0.9533
Fish Toxicity	High FHMT	0.9506
Tetrahymena Pyriformis Toxicity	High TPT	0.9514
Honey Bee Toxicity	High HBT	0.8000
Biodegradation	Not ready biodegradable	0.7479
Acute Oral Toxicity	II	0.5601
Carcinogenicity (Three-class)	Non-required	0.3731

Model	Value	Unit
Absorption
Aqueous solubility	-3.5997	LogS
Caco-2 Permeability	1.0775	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	2.8986	LD50, mol/kg
Fish Toxicity	-0.3381	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	0.4482	pIGC50, ug/L

Targets

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 ]