Lyngbyatoxin A (T3D4088)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (2)XML
Targets (2)
Record Information
Version2.0
Creation Date2014-08-29 05:05:36 UTC
Update Date2014-12-24 20:26:38 UTC
Accession NumberT3D4088
Identification
Common NameLyngbyatoxin A
ClassSmall Molecule
DescriptionLyngbyatoxin A is a cyanotoxin produced by certain cyanobacteria species, notably Moorea producens (formerly classified as Lyngbya majuscula). It is used as a defensive secretion to protect this cyanobacteria from predation by fish, being a potent irritant and vesicant, as well as a carcinogen. Low concentrations more commonly encountered cause milder symptoms, known as seaweed dermatitis. The toxin is highly inflammatory and vesicatory. It is also a strong tumor promoter through activation of protein kinase C.
Compound Type
  • Amine
  • Bacterial Toxin
  • Marine Toxin
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
Lyngbyatoxin A
Lyngbyatoxin-a
Chemical FormulaC27H39N3O2
Average Molecular Mass437.618 g/mol
Monoisotopic Mass437.304 g/mol
CAS Registry Number70497-14-2
IUPAC Name5-(3,7-dimethylocta-1,6-dien-3-yl)-13-(hydroxymethyl)-9-methyl-10-(propan-2-yl)-3,9,12-triazatricyclo[6.6.1.0⁴,¹⁵]pentadeca-1,4,6,8(15),11-pentaen-11-ol
Traditional Nameteleocidin
SMILESCC(C)C1N(C)C2=C3C(CC(CO)N=C1O)=CNC3=C(C=C2)C(C)(CCC=C(C)C)C=C
InChI IdentifierInChI=1/C27H39N3O2/c1-8-27(6,13-9-10-17(2)3)21-11-12-22-23-19(15-28-24(21)23)14-20(16-31)29-26(32)25(18(4)5)30(22)7/h8,10-12,15,18,20,25,28,31H,1,9,13-14,16H2,2-7H3,(H,29,32)
InChI KeyInChIKey=KISDGNGREAJPQR-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acid amides
Alternative Parents
Substituents
  • Alpha-amino acid amide
  • Aromatic monoterpenoid
  • Monoterpenoid
  • 3-alkylindole
  • Indole
  • Indole or derivatives
  • Tertiary aliphatic/aromatic amine
  • Dialkylarylamine
  • Benzenoid
  • Heteroaromatic compound
  • Pyrrole
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Lactam
  • Organoheterocyclic compound
  • Azacycle
  • Alcohol
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organic oxide
  • Organopnictogen compound
  • Primary alcohol
  • Carbonyl group
  • Organic oxygen compound
  • Amine
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoskeleton
  • Cytosol
  • Extracellular
  • Membrane
  • Plasma Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Gastrointestinal Tract
  • Skin
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
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 Solubility0.0044 g/LALOGPS
logP5.22ALOGPS
logP5.72ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)3.15ChemAxon
pKa (Strongest Basic)5.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area71.85 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity134.77 m³·mol⁻¹ChemAxon
Polarizability51.83 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0079-0001900000-47ca9a5fc38221a10e302016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-2008900000-07ddf06d667f9a4cd0322016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0159-4090000000-c80bf387fcd95f94e8082016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-1001900000-5087fd612041caf4e6992016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00kr-0002900000-6460543ef4ef58ccff5e2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-052f-9003000000-72fabe723e8c7d95ad042016-08-03View Spectrum
Toxicity Profile
Route of ExposureDermal; ingestion
Mechanism of ToxicityLyngbyatoxin A is a tumor promoter. Lyngbyatoxin A and related compounds bind to the cysteine-rich C1 domains (C1A and C1B) of protein kinase C (PKC) isozymes to activate them, possibly leading to tumor formation (7). In cancer cells, PKC isozymes are involved in cell proliferation, survival, invasion, migration, apoptosis, angiogenesis, and anticancer drug resistance through their increased or decreased participation in various cellular signaling pathways (8). Lyngbyatoxin A also induces ornithine decarboxylase (2). The ornithine decarboxylation reaction catalyzed by ornithine decarboxylase (ODC) is the first and committed step in the synthesis of polyamines, particularly putrescine, spermidine and spermine. ODC is upregulated in a wide variety of cancers. The mechanism by which ODC promotes carcinogenesis is complex and not entirely known. Along with their direct effect on DNA stability, polyamines also upregulate gap junction genes and downregulate tight junction genes. Gap junction genes are involved in communication between carcinogenic cells and tight junction genes act as tumor suppressors. (Wikipedia)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC.
Uses/SourcesLyngbyatoxin A is a cyanotoxin produced by certain cyanobacteria species, notably Moorea producens (formerly classified as Lyngbya majuscula). It is used as a defensive secretion to protect this cyanobacteria from predation by fish, being a potent irritant and vesicant, as well as a carcinogen. The toxin is highly inflammatory and vesicatory.
Minimum Risk LevelNot Available
Health EffectsLyngbyatoxin A is known as the causative agent of 'swimmer’s itch' with its highly inflammatory effect (7). Lyngbyatoxin A is a potent irritant and vesicant, as well as a carcinogen. Low concentrations more commonly encountered cause milder symptoms, known as seaweed dermatitis. (Wikipedia)
SymptomsInflammation of the skin, blistering.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID3979
ChEMBL IDCHEMBL581451
ChemSpider ID3841
KEGG IDC15720
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
MSDSNot Available
General References
  1. Cardellina JH 2nd, Marner FJ, Moore RE: Seaweed dermatitis: structure of lyngbyatoxin A. Science. 1979 Apr 13;204(4389):193-5. [107586 ]
  2. Fujiki H, Mori M, Nakayasu M, Terada M, Sugimura T, Moore RE: Indole alkaloids: dihydroteleocidin B, teleocidin, and lyngbyatoxin A as members of a new class of tumor promoters. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3872-6. [6791164 ]
  3. Kozikowski AP, Shum PW, Basu A, Lazo JS: Synthesis of structural analogues of lyngbyatoxin A and their evaluation as activators of protein kinase C. J Med Chem. 1991 Aug;34(8):2420-30. [1875340 ]
  4. Zhang FS, Yamasaki S, Kimura K: Rare earth element content in various waste ashes and the potential risk to Japanese soils. Environ Int. 2001 Nov;27(5):393-8. [11757853 ]
  5. Ito E, Satake M, Yasumoto T: Pathological effects of lyngbyatoxin A upon mice. Toxicon. 2002 May;40(5):551-6. [11821127 ]
  6. Edwards DJ, Gerwick WH: Lyngbyatoxin biosynthesis: sequence of biosynthetic gene cluster and identification of a novel aromatic prenyltransferase. J Am Chem Soc. 2004 Sep 22;126(37):11432-3. [15366877 ]
  7. Jiang W, Zhou W, Uchida H, Kikumori M, Irie K, Watanabe R, Suzuki T, Sakamoto B, Kamio M, Nagai H: A new lyngbyatoxin from the Hawaiian cyanobacterium Moorea producens. Mar Drugs. 2014 May 12;12(5):2748-59. doi: 10.3390/md12052748. [24824022 ]
  8. Kang, JH. Protein Kinase C (PKC) Isozymes and Cancer. New Journal of Science. Volume 2014 (2014), Article ID 231418. http://dx.doi.org/10.1155/2014/231418 [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Ornithine decarboxylase
General Function:
Protein homodimerization activity
Specific Function:
Key enzyme of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine.
Gene Name:
ODC1
Uniprot ID:
P11926
Molecular Weight:
51147.73 Da
References
  1. Fujiki H, Mori M, Nakayasu M, Terada M, Sugimura T, Moore RE: Indole alkaloids: dihydroteleocidin B, teleocidin, and lyngbyatoxin A as members of a new class of tumor promoters. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3872-6. [6791164 ]
2. Protein kinase C (Protein Group)
General Function:
Zinc ion binding
Specific Function:
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription.
Included Proteins:
P17252 , P05771 , Q05655 , Q02156 , P05129 , P41743 , Q04759 , Q05513
References
  1. Jiang W, Zhou W, Uchida H, Kikumori M, Irie K, Watanabe R, Suzuki T, Sakamoto B, Kamio M, Nagai H: A new lyngbyatoxin from the Hawaiian cyanobacterium Moorea producens. Mar Drugs. 2014 May 12;12(5):2748-59. doi: 10.3390/md12052748. [24824022 ]