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Record Information
Version2.0
Creation Date2014-09-08 02:38:59 UTC
Update Date2014-12-24 20:26:54 UTC
Accession NumberT3D4636
Identification
Common Name1,2-Naphthoquinone
ClassSmall Molecule
Description1,2-Naphthoquinone or ortho-naphthoquinone is a polycyclic aromatic organic compound with formula C10H6O2. This double ketone (quinone) is a reactive metabolite of naphthalene and is found in diesel exhaust particles. The accumulation of this toxic metabolite in rats from doses of naphthalene has been shown to cause eye damage, including the formation of cataracts. Naphthalene is a constituent of jet fuel, diesel fuel and cigarette smoke. It is also a byproduct of incomplete combustion and hence is an ubiquitous environmental pollutant. The typical air concentration of naphthalene in cities is about 0.18 ppb.
Compound Type
  • Cigarette Toxin
  • Ester
  • Fuel
  • Organic Compound
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1,2-Dihydro-1,2-diketo-naphthalene
1,2-Naphthalenedione
beta-Naphthoquinone
o-Naphthoquinone
ortho-naphthoquinone
Chemical FormulaC10H6O2
Average Molecular Mass158.153 g/mol
Monoisotopic Mass158.037 g/mol
CAS Registry Number524-42-5
IUPAC Name1,2-dihydronaphthalene-1,2-dione
Traditional Name1,2-naphthoquinone
SMILESO=C1C=CC2=CC=CC=C2C1=O
InChI IdentifierInChI=1S/C10H6O2/c11-9-6-5-7-3-1-2-4-8(7)10(9)12/h1-6H
InChI KeyInChIKey=KETQAJRQOHHATG-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as naphthoquinones. Naphthoquinones are compounds containing a naphthohydroquinone moiety, which consists of a benzene ring linearly fused to a bezene-1,4-dione (quinone).
KingdomOrganic compounds
Super ClassBenzenoids
ClassNaphthalenes
Sub ClassNaphthoquinones
Direct ParentNaphthoquinones
Alternative Parents
Substituents
  • Naphthoquinone
  • Aryl ketone
  • Quinone
  • Cyclic ketone
  • Ketone
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytosol
  • Endoplasmic reticulum
  • Extracellular
  • Membrane
  • Microsome
  • Mitochondrial Membrane
  • Mitochondrion
  • Nuclear Membrane
  • Plasma Membrane
  • Soluble Fraction
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
Naphthalene DegradationNot AvailableNot Available
Cell cycleNot Availablemap04110
Antifungal AgentsNot AvailableNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.87 g/LALOGPS
logP1.6ALOGPS
logP2.21ChemAxon
logS-2.3ALOGPS
pKa (Strongest Basic)-8.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area34.14 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity46.16 m³·mol⁻¹ChemAxon
Polarizability15.48 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0f89-1900000000-42c8f89b2ecaa0f83a95JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0900000000-fdec458a61dbf43aca2eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-0900000000-a25a988c2ca6f8139e4bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0zfr-4900000000-f08cdd3ed77583e2d511JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0900000000-15de94554910b64fef7aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0900000000-3ad946808075a5b4a874JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0pb9-0900000000-97d16db55cbe2217eec6JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0900000000-6d3211f5b01d2864ea9bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a59-0900000000-63a86989a211a2574094JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0fb9-9400000000-2b2b703729f00c21ecf9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0900000000-3f5765b536b8e874a7deJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0900000000-833b0d0cdbc4ad8a6c16JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a6r-2900000000-69674abdba6e23e4f592JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0ue9-5900000000-69fae954804ba19712efJSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of Toxicity1,2-Naphthoquinone is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
MetabolismParaoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of OP exposure.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsAcute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
SymptomsSymptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.
TreatmentIf the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID10667
ChEMBL IDCHEMBL52347
ChemSpider ID10217
KEGG IDC14783
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D4636.pdf
General References
  1. Waidyanatha S, Rappaport SM: Hemoglobin and albumin adducts of naphthalene-1,2-oxide, 1,2-naphthoquinone and 1,4-naphthoquinone in Swiss Webster mice. Chem Biol Interact. 2008 Mar 27;172(2):105-14. doi: 10.1016/j.cbi.2008.01.004. Epub 2008 Jan 16. [18291356 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Serine hydrolase activity
Specific Function:
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:
ACHE
Uniprot ID:
P22303
Molecular Weight:
67795.525 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.32 uMNot AvailableBindingDB 22851
References
  1. Hyatt JL, Wadkins RM, Tsurkan L, Hicks LD, Hatfield MJ, Edwards CC, Ross CR 2nd, Cantalupo SA, Crundwell G, Danks MK, Guy RK, Potter PM: Planarity and constraint of the carbonyl groups in 1,2-diones are determinants for selective inhibition of human carboxylesterase 1. J Med Chem. 2007 Nov 15;50(23):5727-34. Epub 2007 Oct 17. [17941623 ]
General Function:
Methylumbelliferyl-acetate deacetylase activity
Specific Function:
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Shows high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and 6-monoacetylmorphine.
Gene Name:
CES2
Uniprot ID:
O00748
Molecular Weight:
61806.41 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory2.4 uMNot AvailableBindingDB 22851
References
  1. Hyatt JL, Wadkins RM, Tsurkan L, Hicks LD, Hatfield MJ, Edwards CC, Ross CR 2nd, Cantalupo SA, Crundwell G, Danks MK, Guy RK, Potter PM: Planarity and constraint of the carbonyl groups in 1,2-diones are determinants for selective inhibition of human carboxylesterase 1. J Med Chem. 2007 Nov 15;50(23):5727-34. Epub 2007 Oct 17. [17941623 ]
General Function:
Transcriptional activator activity, rna polymerase ii transcription factor binding
Specific Function:
Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells.
Gene Name:
CREB1
Uniprot ID:
P16220
Molecular Weight:
36687.86 Da
References
  1. Endo A, Sumi D, Iwamoto N, Kumagai Y: Inhibition of DNA binding activity of cAMP response element-binding protein by 1,2-naphthoquinone through chemical modification of Cys-286. Chem Biol Interact. 2011 Jul 15;192(3):272-7. doi: 10.1016/j.cbi.2011.04.003. Epub 2011 Apr 20. [21530497 ]
General Function:
Ubiquitin binding
Specific Function:
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Gene Name:
TOP2A
Uniprot ID:
P11388
Molecular Weight:
174383.88 Da
References
  1. Gurbani D, Kukshal V, Laubenthal J, Kumar A, Pandey A, Tripathi S, Arora A, Jain SK, Ramachandran R, Anderson D, Dhawan A: Mechanism of inhibition of the ATPase domain of human topoisomerase IIalpha by 1,4-benzoquinone, 1,2-naphthoquinone, 1,4-naphthoquinone, and 9,10-phenanthroquinone. Toxicol Sci. 2012 Apr;126(2):372-90. doi: 10.1093/toxsci/kfr345. Epub 2012 Jan 4. [22218491 ]
General Function:
Protein tyrosine/threonine phosphatase activity
Specific Function:
Dual specificity phosphatase that dephosphorylates MAP kinase MAPK1/ERK2 on both 'Thr-183' and 'Tyr-185', regulating its activity during the meiotic cell cycle.
Gene Name:
DUSP1
Uniprot ID:
P28562
Molecular Weight:
39297.37 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5018.379 uMNot AvailableBindingDB 22851
IC5022.486 uMNot AvailableBindingDB 22851
IC5036.448 uMNot AvailableBindingDB 22851
IC50>50000 uMNot AvailableBindingDB 22851
References
  1. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
General Function:
Peptidyl-cysteine s-nitrosylase activity
Specific Function:
Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.
Gene Name:
GAPDH
Uniprot ID:
P04406
Molecular Weight:
36053.0 Da
References
  1. Miura T, Kakehashi H, Shinkai Y, Egara Y, Hirose R, Cho AK, Kumagai Y: GSH-mediated S-transarylation of a quinone glyceraldehyde-3-phosphate dehydrogenase conjugate. Chem Res Toxicol. 2011 Nov 21;24(11):1836-44. doi: 10.1021/tx200025y. Epub 2011 Sep 1. [21827172 ]
General Function:
Triglyceride lipase activity
Specific Function:
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate.
Gene Name:
CES1
Uniprot ID:
P23141
Molecular Weight:
62520.62 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.93 uMNot AvailableBindingDB 22851
References
  1. Hyatt JL, Wadkins RM, Tsurkan L, Hicks LD, Hatfield MJ, Edwards CC, Ross CR 2nd, Cantalupo SA, Crundwell G, Danks MK, Guy RK, Potter PM: Planarity and constraint of the carbonyl groups in 1,2-diones are determinants for selective inhibition of human carboxylesterase 1. J Med Chem. 2007 Nov 15;50(23):5727-34. Epub 2007 Oct 17. [17941623 ]
General Function:
Ubiquitin protein ligase binding
Specific Function:
Involved in redox regulation of the cell. Can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides. May play a role in the regulation of phospholipid turnover as well as in protection against oxidative injury.
Gene Name:
PRDX6
Uniprot ID:
P30041
Molecular Weight:
25034.715 Da
References
  1. Takayama N, Iwamoto N, Sumi D, Shinkai Y, Tanaka-Kagawa T, Jinno H, Kumagai Y: Peroxiredoxin 6 is a molecular target for 1,2-naphthoquinone, an atmospheric electrophile, in human pulmonary epithelial A549 cells. J Toxicol Sci. 2011;36(6):817-21. [22129745 ]
General Function:
Transmembrane receptor protein tyrosine phosphatase activity
Specific Function:
Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN. Dephosphorylates LYN, and thereby modulates LYN activity (By similarity).
Gene Name:
PTPRC
Uniprot ID:
P08575
Molecular Weight:
147253.075 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC503 uMNot AvailableBindingDB 22851
References
  1. Urbanek RA, Suchard SJ, Steelman GB, Knappenberger KS, Sygowski LA, Veale CA, Chapdelaine MJ: Potent reversible inhibitors of the protein tyrosine phosphatase CD45. J Med Chem. 2001 May 24;44(11):1777-93. [11356112 ]
General Function:
Zinc ion binding
Specific Function:
Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET.
Gene Name:
PTPN1
Uniprot ID:
P18031
Molecular Weight:
49966.44 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC501.64 uMNot AvailableBindingDB 22851
References
  1. Ahn JH, Cho SY, Ha JD, Chu SY, Jung SH, Jung YS, Baek JY, Choi IK, Shin EY, Kang SK, Kim SS, Cheon HG, Yang SD, Choi JK: Synthesis and PTP1B inhibition of 1,2-naphthoquinone derivatives as potent anti-diabetic agents. Bioorg Med Chem Lett. 2002 Aug 5;12(15):1941-6. [12113814 ]