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Record Information
Version3.6
Creation Date2012-09-06 15:16:51 UTC
Update Date2013-02-09 00:33:17 UTC
HMDB IDHMDB15249
Secondary Accession NumbersNone
Metabolite Identification
Common NameAtovaquone
DescriptionAtovaquone 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 fully 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 result in indirect inhibition of these enzymes. The ultimate 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
Thumb
SynonymsNot Available
Chemical FormulaC22H19ClO3
Average Molecular Weight366.837
Monoisotopic Molecular Weight366.102272181
IUPAC Name2-hydroxy-3-[(1r,4r)-4-(4-chlorophenyl)cyclohexyl]-1,4-dihydronaphthalene-1,4-dione
Traditional IUPAC Nameatovaquone
CAS Registry Number95233-18-4
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 KeyKUCQYCKVKVOKAY-CTYIDZIISA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Homomonocyclic Compounds
ClassAcenes
Sub ClassNaphthalenes
Other Descriptors
  • Aromatic Homomonocyclic Compounds
  • Aromatic Homopolycyclic Compounds
  • naphthoquinone(ChEBI)
  • organochlorine compound(ChEBI)
Substituents
  • Aryl Chloride
  • Benzoquinone
  • Chlorobenzene
  • Cyclohexane
  • Enol
  • Ketone
  • Organochloride
Direct ParentNaphthoquinones
Ontology
StatusExpected and Not Quantified
Origin
  • Drug
Biofunction
  • Anti-Infective Agents
  • Antifungal Agents
  • Antimalarials
  • Antiprotozoal Agents
  • Enzyme Inhibitors
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility7.96e-04 g/LNot Available
LogP5.8Not Available
Predicted Properties
PropertyValueSource
water solubility7.960E-04 g/LALOGPS
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 area54.37ChemAxon
rotatable bond count2ChemAxon
refractivity103.11ChemAxon
polarizability39.55ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01117
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01117
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01117
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID10482034
KEGG Compound IDC06835
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkAtovaquone
NuGOwiki LinkHMDB15249
Metagene LinkHMDB15249
METLIN IDNot Available
PubChem CompoundNot Available
PDB IDNot Available
ChEBI ID575568
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot 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. Epub 2009 Nov 24. Pubmed: 19934256