FRCD

Common Name	Sphondin(F03906)
2D Structure
Description	A furanocoumarin derivative isolated from Heracleum laciniatum (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	F03906
CAS Number	483-66-9
PubChem CID	108104
Formula	C12H8O4
IUPAC Name	6-methoxyfuro[2,3-h]chromen-2-one
InChI Key	DLCJNIBLOSKIQW-UHFFFAOYSA-N
InChI	InChI=1S/C12H8O4/c1-14-9-6-7-2-3-10(13)16-11(7)8-4-5-15-12(8)9/h2-6H,1H3
Canonical SMILES	COC1=C2C(=C3C(=C1)C=CC(=O)O3)C=CO2
Isomeric SMILES	COC1=C2C(=C3C(=C1)C=CC(=O)O3)C=CO2
Synonyms	Sphondin 483-66-9 6-Methoxyfuro[2,3-h]chromen-2-one CHEBI:81486 2H-Furo(2,3-h)-1-benzopyran-2-one, 6-methoxy- 6-Methoxy-2H-furo[2,3-H]chromen-2-one Sfondin Spectrum_000598 SpecPlus_000144 Spectrum2_001759
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	216.192
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	1
Complexity	325
Monoisotopic Mass	216.042
Exact Mass	216.042
XLogP	2.2
Formal Charge	0
Heavy Atom Count	16
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+	0.9211
Human Intestinal Absorption	HIA+	0.9921
Caco-2 Permeability	Caco2+	0.6185
P-glycoprotein Substrate	Non-substrate	0.5518
P-glycoprotein Inhibitor	Inhibitor	0.5000
P-glycoprotein Inhibitor	Inhibitor	0.5468
Renal Organic Cation Transporter	Non-inhibitor	0.8178
Distribution
Subcellular localization	Mitochondria	0.6431
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.7921
CYP450 2D6 Substrate	Non-substrate	0.9116
CYP450 3A4 Substrate	Non-substrate	0.6236
CYP450 1A2 Inhibitor	Inhibitor	0.9629
CYP450 2C9 Inhibitor	Non-inhibitor	0.5968
CYP450 2D6 Inhibitor	Inhibitor	0.8932
CYP450 2C19 Inhibitor	Inhibitor	0.9316
CYP450 3A4 Inhibitor	Inhibitor	0.7740
CYP Inhibitory Promiscuity	High CYP Inhibitory Promiscuity	0.7381
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9563
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.9638
AMES Toxicity	AMES toxic	0.8860
Carcinogens	Non-carcinogens	0.9552
Fish Toxicity	High FHMT	0.9401
Tetrahymena Pyriformis Toxicity	High TPT	0.9849
Honey Bee Toxicity	High HBT	0.8252
Biodegradation	Not ready biodegradable	0.7255
Acute Oral Toxicity	III	0.7930
Carcinogenicity (Three-class)	Warning	0.5533

Model	Value	Unit
Absorption
Aqueous solubility	-3.5238	LogS
Caco-2 Permeability	0.8187	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	2.4054	LD50, mol/kg
Fish Toxicity	-0.1047	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	0.5977	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 ]