SAFROLE

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 Search

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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8824955 | https://www.ncbi.nlm.nih.gov/pubmed/18938230 | https://ntp.niehs.nih.gov/ntp/roc/content/profiles/safrole.pdf | https://www.ncbi.nlm.nih.gov/pubmed/18938230 | https://www.ncbi.nlm.nih.gov/pubmed/24132706

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

Targets

Primary Target	Pharmacology	Potency
DNA 278 Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18938230	Interacts 323
Cytochrome P450 1A2 72 Target ID: P05177 Gene ID: 1544.0 Gene Symbol: CYP1A2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15778010	Inhibitor 8297	5.7 µM [IC50]
Cytochrome P450 2A6 16 Target ID: P11509\|\|\|Q4VAU1 Gene ID: 1548.0 Gene Symbol: CYP2A6 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15778010	Inhibitor 8297	12.0 µM [IC50]
Cytochrome P450 2E1 25 Target ID: P05181 Gene ID: 1571.0 Gene Symbol: CYP2E1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15778010	Inhibitor 8297	1.7 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Diabetes mellitus 91 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24132706	Primary		Preclinical	Unknown Approved Use Unknown
Cancer 592 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24150866 https://www.ncbi.nlm.nih.gov/pubmed/21591240	Primary		Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
[Analysis of volatile constituents of root and rhizome of Asarum heterotropoides Fr. var. mandshuricum (Maxim.) Kitag. by gas chromatography-mass spectrometry].	2002 Sep	16358706
[Study on GC fingerprint of the constituents in Herba Asari].	2004 May	15706889
Safrole oxide induces apoptosis in A549 human lung cancer cells.	2004 Sep	15524402
The chemical composition of some Lauraceae essential oils and their antifungal activities.	2004 Sep	15478207
Human cytochrome p450 enzyme specificity for bioactivation of safrole to the proximate carcinogen 1'-hydroxysafrole.	2004 Sep	15377158
Conformationally induced electrostatic stabilization of persulfoxides: a new suggestion for inhibition of physical quenching of singlet oxygen by remote functional groups.	2005 Aug 24	16104760
Expeditious synthesis of bioactive allylphenol constituents of the genus Piper through a metal-free photoallylation procedure.	2005 Aug 7	16032365
A study of impurities in intermediates and 3,4-methylenedioxymethamphetamine (MDMA) samples produced via reductive amination routes.	2005 Dec 20	16226151
Basic and neutral route specific impurities in MDMA prepared by different synthesis methods. Comparison of impurity profiles.	2005 Dec 20	16226147
Safrole-DNA adducts in tissues from esophageal cancer patients: clues to areca-related esophageal carcinogenesis.	2005 Jan 3	15661610
Independent [Ca2+]i increases and cell proliferation induced by the carcinogen safrole in human oral cancer cells.	2005 Jul	16080004
An experimental study of sexual function improving effect of Myristica fragrans Houtt. (nutmeg).	2005 Jul 20	16033651
Probing the mechanism of sulfoxide-catalyzed hemiacetal activation in dehydrative glycosylation.	2005 Jul 22	16018673
Increased sulfur precursors and volatiles production by the leek Allium porrum in response to specialist insect attack.	2005 Jun	16222772
Inhibition of human cytochrome P450 enzymes by the natural hepatotoxin safrole.	2005 May	15778010
'Non-covalent synthesis' of a chiral host of calix[6]arene and enantiomeric discrimination.	2005 May	15751023
Nutmeg intoxication in Texas, 1998-2004.	2005 Nov	16323572
A traditional method of Cinnamomum carolinense preparation eliminates safrole from a therapeutic Pohnpean tea.	2005 Nov 14	16109467
Upregulating of Fas, integrin beta4 and P53 and depressing of PC-PLC activity and ROS level in VEC apoptosis by safrole oxide.	2005 Oct 24	16225864
Assessing susceptibility from early-life exposure to carcinogens.	2005 Sep	16140616
Synthesis and spectroscopic behavior of highly luminescent Eu(3+)-dibenzoylmethanate (DBM) complexes with sulfoxide ligands.	2005 Sep	16043059
Neopetrosiamides, peptides from the marine sponge Neopetrosia sp. that inhibit amoeboid invasion by human tumor cells.	2005 Sep 15	16146380
Safrole-induced Ca2+ mobilization and cytotoxicity in human PC3 prostate cancer cells.	2006	16777715
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	16702019
Co-lyophilization with D-proline greatly enhances peroxidase's stereoselectivity in a non-aqueous medium.	2006 Apr	16614892
The sulphoxidation of S-carboxymethyl-L-cysteine in COPD.	2006 Apr	16585098
Safrole oxide induces apoptosis by up-regulating Fas and FasL instead of integrin beta4 in A549 human lung cancer cells.	2006 Apr 1	16326105
Abuse of nutmeg (Myristica fragrans Houtt.): studies on the metabolism and the toxicologic detection of its ingredients elemicin, myristicin, and safrole in rat and human urine using gas chromatography/mass spectrometry.	2006 Aug	16885726
Safrole-induced cellular Ca2+ increases and death in human osteosarcoma cells.	2006 Aug	16621588
Aryl sulfoxide radical cations. Generation, spectral properties, and theoretical calculations.	2006 Aug 17	16898698
Design and synthesis of 3,4-methylenedioxy-6-nitrophenoxyacetylhydrazone derivatives obtained from natural safrole: new lead-agents with analgesic and antipyretic properties.	2006 Dec 1	16904329
Thioether sulfur oxygenation from O2 or H2O2 reactivity of copper complexes with tridentate N2Sthioether ligands.	2006 Dec 11	17140215
Synthesis by-products from the Wacker oxidation of safrole in methanol using rho-benzoquinone and palladium chloride.	2006 Dec 20	16442765
Safrole oxide induced human umbilical vein vascular endothelial cell differentiation into neuron-like cells by depressing the reactive oxygen species level at the low concentration.	2006 Feb	16473419
Do ion tethered functional groups affect IL solvent properties? The case of sulfoxides and sulfones.	2006 Feb 14	16446838
Conformational arm-wrestling: battles for stereochemical control in benzamides bearing matched and mismatched chiral 2- and 6-substituents.	2006 Feb 7	16446801
Theory and use of the pseudophase model in gas-liquid chromatographic enantiomeric separations.	2006 Jan 1	16383317
Safrole oxide induces apoptosis by activating caspase-3, -8, and -9 in A549 human lung cancer cells.	2006 Jan 1	16242324
[Analysis of disulfoton sulfoxide in chingentsuai by pulsed splitless mass spectrometry using programmed temperature vaporization (PTV) inlet].	2006 Jun	16862987
Identification of an indole series of prostaglandin D2 receptor antagonists.	2006 Jun 1	16529930
Racemic and chiral sulfoxides as potential prodrugs of the COX-2 inhibitors Vioxx and Arcoxia.	2006 Jun 15	16616494
[Comparing analysis of components in volatile oils of nutmeg and prepared nutmeg by GC-MS].	2006 May	17048680
Genotoxicity and endoreduplication inducing activity of the food flavouring eugenol.	2006 May	16595588
Use of biomonitoring data to evaluate methyl eugenol exposure.	2006 Nov	17107870
Phototoxicity testing by online irradiation and HPLC.	2006 Nov	17058072
Illuminating cancer health disparities using ethnogenetic layering (EL) and phenotype segregation network analysis (PSNA).	2006 Spring	17020506
Safrole oxide induces neuronal apoptosis through inhibition of integrin beta4/SOD activity and elevation of ROS/NADPH oxidase activity.	2007 Feb 20	17188719
Antiproliferative and pro-apoptotic activity of eugenol-related biphenyls on malignant melanoma cells.	2007 Jan 18	17233906
Elevated expression of NF-kappaB in oral submucous fibrosis--evidence for NF-kappaB induction by safrole in human buccal mucosal fibroblasts.	2007 Jul	16996785
Synthesis and antitumour evaluation of peptidyl-like derivatives containing the 1,3-benzodioxole system.	2007 Mar	17175071

Patents

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 16 02:16:56 GMT 2023` Edited by `admin` on `Sat Dec 16 02:16:56 GMT 2023`
Record UNII	RSB34337V9
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SAFROLE

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