Mimosine

Common Name

Mimosine Description

Mimosine is only found in individuals that have used or taken this drug. It is an antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca. [PubChem]Mimosine causes inhibition of DNA replication, changes in the progression of the cells in the cell cycle, and apoptosis. Mimosine appears to introduce breaks into DNA. Mimosine is an iron/zinc chelator. Iron depletion induces DNA double-strand breaks in treated cells, and activates a DNA damage response that reslits in focal phosphorylation of histones. This leads to inhibition of DNA replication and/or DNA elongation. Some studies indicate that mimosine prevents the initiation of DNA replication, whereas other studies indicate that mimosine disrupts elongation of the replication fork by impairing deoxyribonucleotide synthesis by inhibiting the activity of the iron-dependent enzyme ribonucleotide reductase and the transcription of the cytoplasmic serine hydroxymethyltransferase gene (SHMT). Inhibition of serine hydroxymethyltransferase is moderated by a zinc responsive unit located in front of the SHMT gene. Structure

Synonyms

Value Source (S)-2-amino-3-(3-Hydroxy-4-oxo-4H-pyridin-1-yl)propanoateChEBI (S)-2-amino-3-(3-Hydroxy-4-oxo-4H-pyridin-1-yl)propanoic acidGenerator L-MimosineHMDB LeucaenineHMDB LeucaenolHMDB LeucenineHMDB LeucenolHMDB MimosinHMDB

Chemical Formlia

C8H10N2O4 Average Molecliar Weight

198.176 Monoisotopic Molecliar Weight

198.064056818 IUPAC Name

(2S)-2-amino-3-(3-hydroxy-4-oxo-1,4-dihydropyridin-1-yl)propanoic acid Traditional Name

mimosine CAS Registry Number

500-44-7 SMILES

N[C@@H](CN1C=CC(=O)C(O)=C1)C(O)=O

InChI Identifier

InChI=1S/C8H10N2O4/c9-5(8(13)14)3-10-2-1-6(11)7(12)4-10/h1-2,4-5,12H,3,9H2,(H,13,14)/t5-/m0/s1

InChI Key

WZNJWVWKTVETCG-YFKPBYRVSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as l-alpha-amino acids. These are alpha amino acids which have the L-configuration of the alpha-carbon atom. Kingdom

Chemical entities Super Class

Organic compounds Class

Organic acids and derivatives Sub Class

Carboxylic acids and derivatives Direct Parent

L-alpha-amino acids Alternative Parents

  • Hydroxypyridines
  • Dihydropyridines
  • Vinylogous amides
  • Heteroaromatic compounds
  • Cyclic ketones
  • Amino acids
  • Monocarboxylic acids and derivatives
  • Carboxylic acids
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organic oxides
  • Monoalkylamines
  • Hydrocarbon derivatives
  • Substituents

  • L-alpha-amino acid
  • Dihydropyridine
  • Hydroxypyridine
  • Hydropyridine
  • Pyridine
  • Heteroaromatic compound
  • Vinylogous amide
  • Amino acid
  • Cyclic ketone
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Azacycle
  • Organoheterocyclic compound
  • Amine
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxide
  • Primary aliphatic amine
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
  • Molecliar Framework

    Aromatic heteromonocyclic compounds External Descriptors

  • non-proteinogenic L-alpha-amino acid (CHEBI:29063 )
  • Ontology Status

    Expected but not Quantified Origin

  • Drug
  • Biofunction

  • Antineoplastic Agents
  • Application

  • Pharmaceutical
  • Cellliar locations

  • Cytoplasm
  • Extracellliar
  • Membrane
  • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point228 °CNot Available Boiling PointNot AvailableNot Available Water Solubility1.31e+01 g/LNot Available LogP-2.5Not Available

    Predicted Properties

    Property Value Source Water Solubility13.1 mg/mLALOGPS logP-2.4ALOGPS logP-3ChemAxon logS-1.2ALOGPS pKa (Strongest Acidic)1.94ChemAxon pKa (Strongest Basic)8.88ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count6ChemAxon Hydrogen Donor Count3ChemAxon Polar Surface Area103.86 Å2ChemAxon Rotatable Bond Count3ChemAxon Refractivity48.66 m3·mol-1ChemAxon Polarizability18.2 Å3ChemAxon Number of Rings1ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Cytoplasm
  • Extracellliar
  • Membrane
  • Biofluid Locations

  • Blood
  • Urine
  • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01055

  • 21059682
  • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01055

  • 21059682
  • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01055 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    389405 KEGG Compound ID

    C04771 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Mimosine NuGOwiki Link

    HMDB15188 Metagene Link

    HMDB15188 METLIN ID

    Not Available PubChem Compound

    440473 PDB ID

    Not Available ChEBI ID

    29063

    Product: GBR 12936

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not Available

    Enzymes

    General function:
    Involved in oxidoreductase activity
    Specific function:
    This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the rate-limiting conversions of tyrosine to DOPA, DOPA to DOPA-quinone and possibly 5,6-dihydroxyindole to indole-5,6 quinone.
    Gene Name:
    TYR
    Uniprot ID:
    P14679
    Molecular weight:
    60392.69
    References
    1. Ahmad VU, Ullah F, Hussain J, Farooq U, Zubair M, Khan MT, Choudhary MI: Tyrosinase inhibitors from Rhododendron collettianum and their structure-activity relationship (SAR) studies. Chem Pharm Bull (Tokyo). 2004 Dec;52(12):1458-61. [PubMed:15577244 ]
    2. Khan KM, Mughal UR, Khan MT, Zia-Ullah, Perveen S, Choudhary MI: Oxazolones: new tyrosinase inhibitors; synthesis and their structure-activity relationships. Bioorg Med Chem. 2006 Sep 1;14(17):6027-33. Epub 2006 Jun 5. [PubMed:16750372 ]
    3. Sugumaran M: Tyrosinase catalyzes an unusual oxidative decarboxylation of 3,4-dihydroxymandelate. Biochemistry. 1986 Aug 12;25(16):4489-92. [PubMed:3094574 ]
    4. Woolery GL, Powers L, Winkler M, Solomon EI, Lerch K, Spiro TG: Extended X-ray absorption fine structure study of the coupled binuclear copper active site of tyrosinase from Neurospora crassa. Biochim Biophys Acta. 1984 Jul 31;788(2):155-61. [PubMed:6234942 ]
    General function:
    Involved in catalytic activity
    Specific function:
    Interconversion of serine and glycine.
    Gene Name:
    SHMT1
    Uniprot ID:
    P34896
    Molecular weight:
    53082.18
    References
    1. Oppenheim EW, Nasrallah IM, Mastri MG, Stover PJ: Mimosine is a cell-specific antagonist of folate metabolism. J Biol Chem. 2000 Jun 23;275(25):19268-74. [PubMed:10766749 ]
    2. Conti P, Frydas S, Reale M, Barbacane RC, Di Gioacchino M, Felaco M, Trakatellis A: Inhibition of MCP-1 and MIP-2 transcription and translation by mimosine in muscle tissue infected with the parasite Trichinella spiralis. Mol Cell Biochem. 2002 Jan;229(1-2):129-37. [PubMed:11936838 ]
    3. Perry C, Sastry R, Nasrallah IM, Stover PJ: Mimosine attenuates serine hydroxymethyltransferase transcription by chelating zinc. Implications for inhibition of DNA replication. J Biol Chem. 2005 Jan 7;280(1):396-400. Epub 2004 Nov 4. [PubMed:15531579 ]
    4. Lin HB, Falchetto R, Mosca PJ, Shabanowitz J, Hunt DF, Hamlin JL: Mimosine targets serine hydroxymethyltransferase. J Biol Chem. 1996 Feb 2;271(5):2548-56. [PubMed:8576220 ]
    General function:
    Involved in chemokine activity
    Specific function:
    Chemotactic factor that attracts monocytes and basophils but not neutrophils or eosinophils. Augments monocyte anti-tumor activity. Has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis or atherosclerosis. May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis
    Gene Name:
    CCL2
    Uniprot ID:
    P13500
    Molecular weight:
    11024.9
    References
    1. Conti P, Frydas S, Reale M, Barbacane RC, Di Gioacchino M, Felaco M, Trakatellis A: Inhibition of MCP-1 and MIP-2 transcription and translation by mimosine in muscle tissue infected with the parasite Trichinella spiralis. Mol Cell Biochem. 2002 Jan;229(1-2):129-37. [PubMed:11936838 ]
    2. Frydas S, Papaioannou N, Papazahariadou M, Hatzistilianou M, Karagouni E, Trakatelli M, Brellou G, Petrarca C, Castellani ML, Conti P, Riccioni G, Patruno A, Grilli A: Inhibition of MCP-1 and MIP-2 chemokines in murine trichinellosis: effect of the anti-inflammatory compound L-mimosine. Int J Immunopathol Pharmacol. 2005 Jan-Mar;18(1):85-94. [PubMed:15698514 ]

    PMID: 21339333