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Identification
NameResveratrol
Accession NumberDB02709  (EXPT02968)
TypeSmall Molecule
GroupsExperimental, Investigational
Description

Resveratrol (3,5,4’-trihydroxystilbene) is a polyphenolic phytoalexin. It is a stilbenoid, a derivate of stilbene, and is produced in plants with the help of the enzyme stilbene synthase. It exists as two structural isomers: cis-(Z) and trans-(E), with the trans-isomer shown in the top image. The trans- form can undergo isomerisation to the cis- form when heated or exposed to ultraviolet irradiation. In a 2004 issue of Science, Dr. Sinclair of Harvard University said resveratrol is not an easy molecule to protect from oxidation. It has been claimed that it is readily degraded by exposure to light, heat, and oxygen. However, studies find that Trans-resveratrol undergoes negligible oxidation in normal atmosphere at room temperature. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
(E)-5-(2-(4-hydroxyphenyl)ethenyl)-1,3-benzenediolNot AvailableNot Available
(E)-5-(p-Hydroxystyryl)resorcinolNot AvailableNot Available
(E)-5-[2-(4-hydroxyphenyl)ethenyl]-1,3-benzendiolNot AvailableNot Available
(E)-5-[2-(4-Hydroxyphenyl)ethenyl]-1,3-benzenediolNot AvailableNot Available
(E)-resveratrolNot AvailableNot Available
3,4',5-StilbenetriolNot AvailableNot Available
3,4',5-trihydroxy-stilbeneNot AvailableNot Available
3,4',5-TrihydroxystilbeneNot AvailableNot Available
trans-3,4',5-trihydroxystilbeneNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number501-36-0
WeightAverage: 228.2433
Monoisotopic: 228.07864425
Chemical FormulaC14H12O3
InChI KeyLUKBXSAWLPMMSZ-OWOJBTEDSA-N
InChI
InChI=1S/C14H12O3/c15-12-5-3-10(4-6-12)1-2-11-7-13(16)9-14(17)8-11/h1-9,15-17H/b2-1+
IUPAC Name
5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol
SMILES
OC1=CC=C(\C=C\C2=CC(O)=CC(O)=C2)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassPhenylpropanoids and Polyketides
ClassStilbenes
SubclassNot Available
Direct parentStilbenes
Alternative parentsStyrenes; Resorcinols; Polyols; Polyamines; Enols
Substituentsresorcinol; styrene; phenol derivative; benzene; polyol; polyamine; enol
Classification descriptionThis compound belongs to the stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
Pharmacology
IndicationBeing investigated for the treatment of Herpes labialis infections (cold sores).
PharmacodynamicsResveratrol, a phytoalexin, has been found to inhibit herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) replication in a dose-dependent, reversible manner, although this is only one of its many pharmaceutical properties. In some countries where there is higher consumption of red wine, there appears to be a lower incidence of heart disease. Other benefits of resveratrol include its anti-inflammatory and antioxidant effects. In preclinical studies, Resveratrol has been found to have potential anticancer properties.
Mechanism of actionResveratrol suppresses NF-kappaB (NF-kappaB) activation in HSV infected cells. Reports have indicated that HSV activates NF-kappaB during productive infection and this may be an essential aspect of its replication scheme [PMID: 9705914].
AbsorptionHigh absorption but very low bioavailability.
Volume of distributionNot Available
Protein bindingStrong affinity towards protein binding.
Metabolism

Hepatic. Rapidly metabolized and excreted.

SubstrateEnzymesProduct
Resveratrol
piceatannol (3,5,3',4'-tetrahydroxystilbene)Details
Resveratrol
tetrahydroxystilbene M1Details
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9952
Blood Brain Barrier + 0.59
Caco-2 permeable + 0.8915
P-glycoprotein substrate Non-substrate 0.6501
P-glycoprotein inhibitor I Non-inhibitor 0.9266
P-glycoprotein inhibitor II Non-inhibitor 0.9612
Renal organic cation transporter Non-inhibitor 0.8634
CYP450 2C9 substrate Non-substrate 0.7519
CYP450 2D6 substrate Non-substrate 0.9288
CYP450 3A4 substrate Non-substrate 0.7143
CYP450 1A2 substrate Inhibitor 0.9106
CYP450 2C9 substrate Inhibitor 0.7068
CYP450 2D6 substrate Non-inhibitor 0.9226
CYP450 2C19 substrate Inhibitor 0.8052
CYP450 3A4 substrate Inhibitor 0.7539
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8559
Ames test Non AMES toxic 0.8407
Carcinogenicity Non-carcinogens 0.7825
Biodegradation Not ready biodegradable 0.8499
Rat acute toxicity 1.6791 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8933
hERG inhibition (predictor II) Non-inhibitor 0.9462
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point254 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.0688ALOGPS
logP2.57ALOGPS
logP3.4ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)8.99ChemAxon
pKa (Strongest Basic)-5.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area60.69 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity67.46 m3·mol-1ChemAxon
Polarizability24.55 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraGC-MS
References
Synthesis Reference

Philippe Jeandet, Roger Bessis, Marielle Adrian, Jean-Claude Yvin, Jean-Marie Joubert, “Use of aluminium chloride as a resveratrol synthesis elicitor.” U.S. Patent US6080701, issued August, 1991.

US6080701
General Reference
  1. Farina A, Ferranti C, Marra C: An improved synthesis of resveratrol. Nat Prod Res. 2006 Mar;20(3):247-52. Pubmed
  2. Renaud S, Ruf JC: The French paradox: vegetables or wine. Circulation. 1994 Dec;90(6):3118-9. Pubmed
  3. Wang Y, Catana F, Yang Y, Roderick R, van Breemen RB: An LC-MS method for analyzing total resveratrol in grape juice, cranberry juice, and in wine. J Agric Food Chem. 2002 Jan 30;50(3):431-5. Pubmed
  4. Lyons MM, Yu C, Toma RB, Cho SY, Reiboldt W, Lee J, van Breemen RB: Resveratrol in raw and baked blueberries and bilberries. J Agric Food Chem. 2003 Sep 24;51(20):5867-70. Pubmed
  5. Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK: High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004 Dec;32(12):1377-82. Epub 2004 Aug 27. Pubmed
  6. Csaki C, Keshishzadeh N, Fischer K, Shakibaei M: Regulation of inflammation signalling by resveratrol in human chondrocytes in vitro. Biochem Pharmacol. 2007 Sep 18;. Pubmed
  7. Docherty JJ, Fu MM, Stiffler BS, Limperos RJ, Pokabla CM, DeLucia AL: Resveratrol inhibition of herpes simplex virus replication. Antiviral Res. 1999 Oct;43(3):145-55. Pubmed
  8. N’ soukpoe-Kossi CN, St-Louis C, Beauregard M, Subirade M, Carpentier R, Hotchandani S, Tajmir-Riahi HA: Resveratrol binding to human serum albumin. J Biomol Struct Dyn. 2006 Dec;24(3):277-83. Pubmed
External Links
ResourceLink
KEGG CompoundC03582
PubChem Compound445154
PubChem Substance46504705
ChemSpider4880
BindingDB23926
ChEBI27881
ChEMBL
Therapeutic Targets DatabaseDNC001205
PharmGKBPA165291843
HETSTL
WikipediaResveratrol
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSshow(16.6 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Ribosyldihydronicotinamide dehydrogenase [quinone]

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Ribosyldihydronicotinamide dehydrogenase [quinone] P16083 Details

References:

  1. Buryanovskyy L, Fu Y, Boyd M, Ma Y, Hsieh TC, Wu JM, Zhang Z: Crystal structure of quinone reductase 2 in complex with resveratrol. Biochemistry. 2004 Sep 14;43(36):11417-26. Pubmed
  2. Wang Z, Hsieh TC, Zhang Z, Ma Y, Wu JM: Identification and purification of resveratrol targeting proteins using immobilized resveratrol affinity chromatography. Biochem Biophys Res Commun. 2004 Oct 22;323(3):743-9. Pubmed

2. Casein kinase II subunit alpha

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Casein kinase II subunit alpha P68400 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Prostaglandin G/H synthase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 1 P23219 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. Prostaglandin G/H synthase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Piver B, Fer M, Vitrac X, Merillon JM, Dreano Y, Berthou F, Lucas D: Involvement of cytochrome P450 1A2 in the biotransformation of trans-resveratrol in human liver microsomes. Biochem Pharmacol. 2004 Aug 15;68(4):773-82. Pubmed
  2. Chang TK, Chen J, Lee WB: Differential inhibition and inactivation of human CYP1 enzymes by trans-resveratrol: evidence for mechanism-based inactivation of CYP1A2. J Pharmacol Exp Ther. 2001 Dec;299(3):874-82. Pubmed

2. Cytochrome P450 1A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

References:

  1. Chang TK, Chen J, Lee WB: Differential inhibition and inactivation of human CYP1 enzymes by trans-resveratrol: evidence for mechanism-based inactivation of CYP1A2. J Pharmacol Exp Ther. 2001 Dec;299(3):874-82. Pubmed
  2. Piver B, Fer M, Vitrac X, Merillon JM, Dreano Y, Berthou F, Lucas D: Involvement of cytochrome P450 1A2 in the biotransformation of trans-resveratrol in human liver microsomes. Biochem Pharmacol. 2004 Aug 15;68(4):773-82. Pubmed

3. Cytochrome P450 1B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1B1 Q16678 Details

References:

  1. Chang TK, Chen J, Lee WB: Differential inhibition and inactivation of human CYP1 enzymes by trans-resveratrol: evidence for mechanism-based inactivation of CYP1A2. J Pharmacol Exp Ther. 2001 Dec;299(3):874-82. Pubmed

4. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Chow HH, Garland LL, Hsu CH, Vining DR, Chew WM, Miller JA, Perloff M, Crowell JA, Alberts DS: Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. Cancer Prev Res (Phila). 2010 Sep;3(9):1168-75. Epub 2010 Aug 17. Pubmed
  2. Piver B, Berthou F, Dreano Y, Lucas D: Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components. Toxicol Lett. 2001 Dec 15;125(1-3):83-91. Pubmed

Carriers

1. Transthyretin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Transthyretin P02766 Details

References:

  1. Commodari F, Khiat A, Ibrahimi S, Brizius AR, Kalkstein N: Comparison of the phytoestrogen trans-resveratrol (3,4’,5-trihydroxystilbene) structures from x-ray diffraction and solution NMR. Magn Reson Chem. 2005 Jul;43(7):567-72. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:18