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Dicentrine (T3D4092)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (2)XML
Targets (2)
Record Information
Version2.0
Creation Date2014-08-29 05:07:05 UTC
Update Date2014-12-24 20:26:38 UTC
Accession NumberT3D4092
Identification
Common NameDicentrine
ClassSmall Molecule
DescriptionDicentrine is an anticancer compound isolated from Lindera, a species of flowering plants.
Compound Type
  • Amine
  • Ether
  • Food Toxin
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
d-Dicentrine
Eximine
O,N-Dimethyllitseferine
Chemical FormulaC20H21NO4
Average Molecular Mass339.385 g/mol
Monoisotopic Mass339.147 g/mol
CAS Registry Number517-66-8
IUPAC Name(12S)-16,17-dimethoxy-11-methyl-3,5-dioxa-11-azapentacyclo[10.7.1.0²,⁶.0⁸,²⁰.0¹⁴,¹⁹]icosa-1(20),2(6),7,14,16,18-hexaene
Traditional Namedicentrine
SMILES[H][C@]12CC3=CC(OC)=C(OC)C=C3C3=C1C(CCN2C)=CC1=C3OCO1
InChI IdentifierInChI=1S/C20H21NO4/c1-21-5-4-11-7-17-20(25-10-24-17)19-13-9-16(23-3)15(22-2)8-12(13)6-14(21)18(11)19/h7-9,14H,4-6,10H2,1-3H3/t14-/m0/s1
InChI KeyInChIKey=YJWBWQWUHVXPNC-AWEZNQCLSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as aporphines. These are quinoline alkaloids containing the dibenzo[de,g]quinoline ring system or a dehydrogenated derivative thereof.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassAporphines
Sub ClassNot Available
Direct ParentAporphines
Alternative Parents
Substituents
  • Aporphine
  • Benzoquinoline
  • Phenanthrene
  • Naphthalene
  • Quinoline
  • Tetrahydroisoquinoline
  • Benzodioxole
  • Anisole
  • Aralkylamine
  • Alkyl aryl ether
  • Benzenoid
  • Tertiary aliphatic amine
  • Tertiary amine
  • Organoheterocyclic compound
  • Azacycle
  • Oxacycle
  • Acetal
  • Ether
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic nitrogen compound
  • Organonitrogen compound
  • Amine
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Extracellular matrix
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Cell cycleNot Availablemap04110
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 Solubility0.08 g/LALOGPS
logP2.76ALOGPS
logP3.01ChemAxon
logS-3.6ALOGPS
pKa (Strongest Basic)7.06ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area40.16 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity94.72 m³·mol⁻¹ChemAxon
Polarizability37.12 ųChemAxon
Number of Rings5ChemAxon
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, Positivesplash10-0006-0009000000-a5de239393bfef9da0a82016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-0029000000-4a28487f76316e86c9e92016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01r6-0090000000-deef7dd6d38cdcc8bc3a2016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0009000000-6c8f5b7b70e9a88729762016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-0019000000-0cd2b177006f7f79a8072016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0ki6-1092000000-e04c5d8a83d378fe17672016-08-03View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityDicentrine was found to be a potent alpha 1-adrenoceptor blocking agent in rat thoracic aorta as revealed by its competitive antagonism of noradrenaline- (pA2 = 8.19 +/- 0.09) or phenylephrine (pA2 = 9.01 +/- 0.10)-induced vasoconstriction. These effects still persisted in denuded aorta. Dicentrine inhibited platelet aggregation and release reaction through the suppression of thromboxane formation and elevation of adenosine 3': S'-cyclic monophosphate. (1) d-Dicentrine significantly inhibits the growth of human hepatoma cell line HuH-7 by delaying its doubling time in tissue culture. An in vitro colony forming assay showed that d-dicentrine decreased the colony formation efficiency in both hepatoma cell lines, HuH-7 and MS-G2. An MTT assay in 21 tumor cell lines also revealed that d-dicentrine was most cytotoxic to esophageal carcinoma HCE-6, lymphoma cell lines Molt-4 and CESS, leukemia cell lines HL60 and K562, and hepatoma cell line MS-G2. (2) Dicentrine is also a selective α1-adrenoceptor antagonist with potent antiarrhythmic and antihypertensive activities. (3)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesDicentrine is an anticancer compound isolated from Lindera, a species of flowering plants.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID101300
ChEMBL IDCHEMBL464748
ChemSpider ID91532
KEGG IDC17426
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. Teng CM, Yu SM, Ko FN, Chen CC, Huang YL, Huang TF: Dicentrine, a natural vascular alpha 1-adrenoceptor antagonist, isolated from Lindera megaphylla. Br J Pharmacol. 1991 Nov;104(3):651-6. [1686739 ]
  2. Huang RL, Chen CC, Huang YL, Ou JC, Hu CP, Chen CF, Chang C: Anti-tumor effects of d-dicentrine from the root of Lindera megaphylla. Planta Med. 1998 Apr;64(3):212-5. [9581516 ]
  3. Lai YC, Kuo TF, Chen CK, Tsai HJ, Lee SS: Metabolism of dicentrine: identification of the phase I and phase II metabolites in miniature pig urine. Drug Metab Dispos. 2010 Oct;38(10):1714-22. doi: 10.1124/dmd.110.033795. Epub 2010 Jul 9. [20622045 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

1. Alpha-1 adrenergic receptors (Protein Group)
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Included Proteins:
P35348 , P35368 , P25100
References
  1. Teng CM, Yu SM, Ko FN, Chen CC, Huang YL, Huang TF: Dicentrine, a natural vascular alpha 1-adrenoceptor antagonist, isolated from Lindera megaphylla. Br J Pharmacol. 1991 Nov;104(3):651-6. [1686739 ]
  2. Lai YC, Kuo TF, Chen CK, Tsai HJ, Lee SS: Metabolism of dicentrine: identification of the phase I and phase II metabolites in miniature pig urine. Drug Metab Dispos. 2010 Oct;38(10):1714-22. doi: 10.1124/dmd.110.033795. Epub 2010 Jul 9. [20622045 ]
Target Details
2. Cyclin-dependent kinase 2
General Function:
Metal ion binding
Specific Function:
Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity).
Gene Name:
CDK2
Uniprot ID:
P24941
Molecular Weight:
33929.215 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>50 uMNot AvailableBindingDB 50306885
References
  1. Hegde VR, Borges S, Pu H, Patel M, Gullo VP, Wu B, Kirschmeier P, Williams MJ, Madison V, Fischmann T, Chan TM: Semi-synthetic aristolactams--inhibitors of CDK2 enzyme. Bioorg Med Chem Lett. 2010 Feb 15;20(4):1384-7. doi: 10.1016/j.bmcl.2010.01.007. Epub 2010 Jan 7. [20097066 ]