U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C10H10O2
Molecular Weight 162.1852
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SAFROLE

SMILES

C=CCC1=CC=C2OCOC2=C1

InChI

InChIKey=ZMQAAUBTXCXRIC-UHFFFAOYSA-N
InChI=1S/C10H10O2/c1-2-3-8-4-5-9-10(6-8)12-7-11-9/h2,4-6H,1,3,7H2

HIDE SMILES / InChI
Molecular Formula C10H10O2
Molecular Weight 162.1852
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Safrole is a natural product obtained from essential oil of the root bark of Sassafras tree. Safrole has been used as a flavoring agent in drugs and in the manufacture of heliotropin, perfumes, soaps, and piperonyl butoxide. Oil of sassafras, which contains safrole, was formerly used to flavor some soft drinks, such as root beer. However, this use or any other addition of safrole or oil of sassafras to food was banned in the United States in 1960 due to evidence of carcinogenicity. Numerous studies have shown that safrole from betel quid-containing safrole might be involved in the pathogenesis of hepatocellular carcinoma in human due to the formation of DNA adducts. Safrole has also been used in the illicit production of the drug 3,4-methylenedioxymethamphetamine (MDMA, or ecstasy), and the U.S. Drug Enforcement Administration has designated safrole a List I Chemical. Anticancer and anti-diabetic properties of safrole were investigated in vitro and in vivo.

Originator

Approval Year

2020
842
Targets

Targets

Primary TargetPharmacologyConditionPotency
DNA
241
Target ID: CHEMBL2311221
Interacts
314
Cytochrome P450 1A2
68
Target ID: P05177
Gene ID: 1544.0
Gene Symbol: CYP1A2
Target Organism: Homo sapiens (Human)
Inhibitor
8146
 5.7 µM [IC50]
Cytochrome P450 2A6
15
Target ID: P11509|||Q4VAU1
Gene ID: 1548.0
Gene Symbol: CYP2A6
Target Organism: Homo sapiens (Human)
Inhibitor
8146
 12.0 µM [IC50]
Cytochrome P450 2E1
25
Target ID: P05181
Gene ID: 1571.0
Gene Symbol: CYP2E1
Target Organism: Homo sapiens (Human)
Inhibitor
8146
 1.7 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Basic research
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Catalytic and immunochemical properties of hepatic cytochrome P450 1A in three avian species treated with beta-naphthoflavone or isosafrole.
2001 Sep
Conservation and diversity of gene families explored using the CODEHOP strategy in higher plants.
2002 Aug 1
Distinction of carcinogens from mutagens by induction of liver cell foci in a model for detection of initiation activity.
2002 Dec 15
Evidence for the involvement of CYP1A2 in the metabolism of bromodichloromethane in rat liver.
2002 Jul 1
Effects of safrole on the defensive functions of human neutrophils.
2003 Apr
In vitro metabolism of fenthion and fenthion sulfoxide by liver preparations of sea bream, goldfish, and rats.
2003 Feb
Concentrations of nine alkenylbenzenes, coumarin, piperonal and pulegone in Indian bidi cigarette tobacco.
2003 Feb
Identification of the main human cytochrome P450 enzymes involved in safrole 1'-hydroxylation.
2004 Aug
Age-related differences in susceptibility to carcinogenesis: a quantitative analysis of empirical animal bioassay data.
2004 Aug
A concise stereocontrolled formal total synthesis of (+/-)-podophyllotoxin using sulfoxide chemistry.
2004 Jan 21
Safrole oxide induces apoptosis in A549 human lung cancer cells.
2004 Sep
The chemical composition of some Lauraceae essential oils and their antifungal activities.
2004 Sep
Human cytochrome p450 enzyme specificity for bioactivation of safrole to the proximate carcinogen 1'-hydroxysafrole.
2004 Sep
Expeditious synthesis of bioactive allylphenol constituents of the genus Piper through a metal-free photoallylation procedure.
2005 Aug 7
Flavonoids and alkenylbenzenes: mechanisms of mutagenic action and carcinogenic risk.
2005 Jul 1
An experimental study of sexual function improving effect of Myristica fragrans Houtt. (nutmeg).
2005 Jul 20
Probing the mechanism of sulfoxide-catalyzed hemiacetal activation in dehydrative glycosylation.
2005 Jul 22
Assessing susceptibility from early-life exposure to carcinogens.
2005 Sep
Determination of synthesis method of ecstasy based on the basic impurities.
2005 Sep 10
Suppressing Akt phosphorylation and activating Fas by safrole oxide inhibited angiogenesis and induced vascular endothelial cell apoptosis in the presence of fibroblast growth factor-2 and serum.
2006
Theory and use of the pseudophase model in gas-liquid chromatographic enantiomeric separations.
2006 Jan 1
Illuminating cancer health disparities using ethnogenetic layering (EL) and phenotype segregation network analysis (PSNA).
2006 Spring
Safrole oxide induces neuronal apoptosis through inhibition of integrin beta4/SOD activity and elevation of ROS/NADPH oxidase activity.
2007 Feb 20
Patents

Patents

05110956
30
06022894
1
06818660
1
JP4813379B2
14
JPH1066536A
2
JPH11197223A
1
JPS6229522A
1

Sample Use Guides

In Vivo Use Guide
As a food additive, safrole was consumed orally. The addition of safrole to food, however, was banned in 1960.
Route of Administration: Oral
In Vitro Use Guide
The ability of safrole to inhibit cytochromes was investigated using recombinant human P450s expressed in E.Coli. Oxidations were initiated by the addition of a NADPH-generating system containing NADP, glucose-6-phosphate, and glucose-6-phosphate dehydrogenase. Duplicated reactions were carried out at 37 C with shaking for 10–20 min. Stock solution of safrole was prepared using methanol and the final content of methanol was less than 1% in the reaction volume of 0.2–1.0 ml. The same amount of methanol was added in the control reactions.
Substance Class Chemical
Created
by admin
on Sat Dec 17 13:59:38 UTC 2022
Edited
by admin
on Sat Dec 17 13:59:38 UTC 2022
Record UNII
RSB34337V9
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SAFROLE
MI  
Systematic Name English
5-(2-PROPENYL)-1,3-BENZODIOXOLE
Systematic Name English
5-PROP-2-ENYL-1,3-BENZODIOXOLE
Systematic Name English
SAFROLE [IARC]
Common Name English
4-ALLYL-1,2-METHYLENEDIOXYBENZENE
Systematic Name English
M-ALLYL PYROCATECHINMETHYLENE ETHER
Common Name English
NSC-11831
Code English
SHIKOMOL
Common Name English
SAFROLE [MI]
Common Name English
SAFROLE [USP-RS]
Common Name English
RHYUNO OIL
Common Name English
BENZENE, 4-ALLYL-1,2-(METHYLENEDIOXY)-
Systematic Name English
1-ALLYL-3,4-METHYLENEDIOXYBENZENE
Systematic Name English
Classification Tree Code System Code
CFR 21 CFR 189.180
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
JECFA EVALUATION SAFROLE AND ISOSAFROLE
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
NCI_THESAURUS C45187
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
Code System Code Type Description
RS_ITEM_NUM
1607299
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
ECHA (EC/EINECS)
202-345-4
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
RXCUI
2383532
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
CHEBI
8994
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
ChEMBL
CHEMBL242273
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
WIKIPEDIA
SAFROLE
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
MERCK INDEX
M9723
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY Merck Index
EVMPD
SUB64305
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
MESH
D012451
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
FDA UNII
RSB34337V9
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
EPA CompTox
DTXSID0021254
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
CAS
94-59-7
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
NCI_THESAURUS
C44443
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
NSC
11831
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
PUBCHEM
5144
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
DAILYMED
RSB34337V9
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
HSDB
2653
Created by admin on Sat Dec 17 13:59:38 UTC 2022 , Edited by admin on Sat Dec 17 13:59:38 UTC 2022
PRIMARY
Related Record Type Details
CINNAMON
PARENT -> CONSTITUENT ALWAYS PRESENT
CINNAMOMUM JAPONICUM WHOLE
PARENT -> CONSTITUENT ALWAYS PRESENT
A cinnamon leaf oil of Chinese origin, Cinnamomun japonicum Sieb., contains a high concentration of safrole (60%) and only about 3% eugenol.
CINNAMON BARK OIL
PARENT -> CONSTITUENT MAY BE PRESENT
ASSAY (GC)
CINNAMON LEAF OIL
PARENT -> CONSTITUENT MAY BE PRESENT
ASSAY (GC)
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966