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Atovaquone

July 24, 2017
Common Name

Atovaquone Description

Atovaquone is only found in individuals that have used or taken this drug. It is a hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols. [PubChem]Atovaquone is a hydroxy- 1, 4- naphthoquinone, an analog of ubiquinone, with antipneumocystis activity. The mechanism of action against Pneumocystis carinii has not been flily elucidated. In Plasmodium species, the site of action appears to be the cytochrome bc1 complex (Complex III). Several metabolic enzymes are linked to the mitochondrial electron transport chain via ubiquinone. Inhibition of electron transport by atovaquone will reslit in indirect inhibition of these enzymes. The litimate metabolic effects of such blockade may include inhibition of nucleic acid and ATP synthesis. Atovaquone also has been shown to have good in vitro activity against Toxoplasma gondii. Structure

MOLSDFPDBSMILESInChI

Synonyms

Value Source 2-(trans-4-(P-Chlorophenyl)cyclohexyl)-3-hydroxy-1,4-naphthoquinoneChEBI AcuvelChEBI MepronChEBI WellvoneChEBI

Chemical Formlia

C22H19ClO3 Average Molecliar Weight

366.837 Monoisotopic Molecliar Weight

366.102272181 IUPAC Name

2-hydroxy-3-[(1r,4r)-4-(4-chlorophenyl)cyclohexyl]-1,4-dihydronaphthalene-1,4-dione Traditional Name

atovaquone CAS Registry Number

95233-18-4 SMILES

OC1=C([C@H]2CC[C@@H](CC2)C2=CC=C(Cl)C=C2)C(=O)C2=CC=CC=C2C1=O

InChI Identifier

InChI=1S/C22H19ClO3/c23-16-11-9-14(10-12-16)13-5-7-15(8-6-13)19-20(24)17-3-1-2-4-18(17)21(25)22(19)26/h1-4,9-13,15,26H,5-8H2/t13-,15-

InChI Key

KUCQYCKVKVOKAY-CTYIDZIISA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as naphthoquinones. These are compounds containing a naphthohydroquinone moiety, which consists of a benzene ring linearly fused to a bezene-1,4-dione (quinone). Kingdom

Chemical entities Super Class

Organic compounds Class

Benzenoids Sub Class

Naphthalenes Direct Parent

Naphthoquinones Alternative Parents

  • Quinones
  • Aryl ketones
  • Chlorobenzenes
  • Aryl chlorides
  • Vinylogous acids
  • Enols
  • Organochlorides
  • Organic oxides
  • Hydrocarbon derivatives

    • Substituents

  • Naphthoquinone
  • Quinone
  • Aryl ketone
  • Chlorobenzene
  • Halobenzene
  • Aryl chloride
  • Monocyclic benzene moiety
  • Aryl halide
  • Vinylogous acid
  • Ketone
  • Enol
  • Organic oxide
  • Organooxygen compound
  • Organochloride
  • Organohalogen compound
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Aromatic homopolycyclic compound

    • Molecliar Framework

    Aromatic homopolycyclic compounds External Descriptors

  • naphthoquinone (CHEBI:575568 )
  • monochlorobenzenes (CHEBI:575568 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anti-Infective Agents
  • Antifungal Agents
  • Antimalarials
  • Antiprotozoal Agents
  • Enzyme Inhibitors

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility7.96e-04 g/LNot Available LogP5.8Not Available

    Predicted Properties

    Property Value Source Water Solubility0.000796 mg/mLALOGPS logP4.74ALOGPS logP5ChemAxon logS-5.7ALOGPS pKa (Strongest Acidic)8.23ChemAxon pKa (Strongest Basic)-4.1ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count3ChemAxon Hydrogen Donor Count1ChemAxon Polar Surface Area54.37 Å2ChemAxon Rotatable Bond Count2ChemAxon Refractivity103.11 m3·mol-1ChemAxon Polarizability39.55 Å3ChemAxon Number of Rings4ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-066r-0968000000-4d83793ef10d849ce35eView in MoNA 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
  • 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 DB01117

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01117

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01117 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

    10482034 KEGG Compound ID

    C06835 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Atovaquone NuGOwiki Link

    HMDB15249 Metagene Link

    HMDB15249 METLIN ID

    Not Available PubChem Compound

    Not Available PDB ID

    Not Available ChEBI ID

    575568

    Product: Bleomycin (sulfate)

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

    Enzymes

    General function:
    Involved in catalytic activity
    Specific function:
    Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
    Gene Name:
    DHODH
    Uniprot ID:
    Q02127
    Molecular weight:
    42866.93
    References
    1. Knecht W, Henseling J, Loffler M: Kinetics of inhibition of human and rat dihydroorotate dehydrogenase by atovaquone, lawsone derivatives, brequinar sodium and polyporic acid. Chem Biol Interact. 2000 Jan 3;124(1):61-76. [PubMed:10658902 ]
    2. Hansen M, Le Nours J, Johansson E, Antal T, Ullrich A, Loffler M, Larsen S: Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain. Protein Sci. 2004 Apr;13(4):1031-42. [PubMed:15044733 ]
    3. Ittarat I, Asawamahasakda W, Bartlett MS, Smith JW, Meshnick SR: Effects of atovaquone and other inhibitors on Pneumocystis carinii dihydroorotate dehydrogenase. Antimicrob Agents Chemother. 1995 Feb;39(2):325-8. [PubMed:7726490 ]
    4. Seymour KK, Lyons SD, Phillips L, Rieckmann KH, Christopherson RI: Cytotoxic effects of inhibitors of de novo pyrimidine biosynthesis upon Plasmodium falciparum. Biochemistry. 1994 May 3;33(17):5268-74. [PubMed:7909690 ]
    5. Seymour KK, Yeo AE, Rieckmann KH, Christopherson RI: dCTP levels are maintained in Plasmodium falciparum subjected to pyrimidine deficiency or excess. Ann Trop Med Parasitol. 1997 Sep;91(6):603-9. [PubMed:9425362 ]
    6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    General function:
    Involved in monooxygenase activity
    Specific function:
    Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
    Gene Name:
    CYP2C9
    Uniprot ID:
    P11712
    Molecular weight:
    55627.365
    References
    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

    PMID: 17786207

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