Hmdb loader
Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2022-03-07 02:51:57 UTC
HMDB IDHMDB0015349
Secondary Accession Numbers
  • HMDB15349
Metabolite Identification
Common NameHalofantrine
DescriptionHalofantrine is a drug used to treat malaria. It belongs to the phenanthrene class of compounds that includes quinine and lumefantrine. It appears to inhibit polymerisation of heme molecules (by the parasite enzyme 'heme polymerase'), resulting in the parasite being poisoned by its own waste. Halofantrine has been shown to preferentially block open and inactivated HERG channels leading to some degree of cardiotoxicity.
Structure
Data?1582753287
Synonyms
ValueSource
Halofantrine hydrochlorideMeSH, HMDB
1-(1,3-dichloro-6-Trifluoromethyl-9-phenanthryl)-3-di(N-butyl)aminopropanol HCLMeSH, HMDB
HalfanMeSH, HMDB
HalofantrineMeSH
Chemical FormulaC26H30Cl2F3NO
Average Molecular Weight500.424
Monoisotopic Molecular Weight499.165654616
IUPAC Name3-(dibutylamino)-1-[1,3-dichloro-6-(trifluoromethyl)phenanthren-9-yl]propan-1-ol
Traditional Namehalofantrine
CAS Registry Number69756-53-2
SMILES
CCCCN(CCCC)CCC(O)C1=C2C=CC(=CC2=C2C=C(Cl)C=C(Cl)C2=C1)C(F)(F)F
InChI Identifier
InChI=1S/C26H30Cl2F3NO/c1-3-5-10-32(11-6-4-2)12-9-25(33)23-16-22-21(14-18(27)15-24(22)28)20-13-17(26(29,30)31)7-8-19(20)23/h7-8,13-16,25,33H,3-6,9-12H2,1-2H3
InChI KeyFOHHNHSLJDZUGQ-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as phenanthrenes and derivatives. These are polycyclic compounds containing a phenanthrene moiety, which is a tricyclic aromatic compound with three non-linearly fused benzene.
KingdomOrganic compounds
Super ClassBenzenoids
ClassPhenanthrenes and derivatives
Sub ClassNot Available
Direct ParentPhenanthrenes and derivatives
Alternative Parents
Substituents
  • Phenanthrene
  • Chloronaphthalene
  • Naphthalene
  • Aralkylamine
  • Aryl chloride
  • Aryl halide
  • 1,3-aminoalcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • Organic nitrogen compound
  • Aromatic alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organochloride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic oxygen compound
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Alcohol
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External DescriptorsNot Available
Ontology
Physiological effectNot Available
Disposition
ProcessNot Available
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.00011 g/LNot Available
LogP8.9Not Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.00011 g/LALOGPS
logP7.34ALOGPS
logP8.06ChemAxon
logS-6.7ALOGPS
pKa (Strongest Acidic)14.47ChemAxon
pKa (Strongest Basic)10.05ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area23.47 ŲChemAxon
Rotatable Bond Count11ChemAxon
Refractivity131.66 m³·mol⁻¹ChemAxon
Polarizability51.53 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityNoChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DeepCCS[M+H]+213.40530932474
DeepCCS[M-H]-211.04630932474
DeepCCS[M-2H]-244.34630932474
DeepCCS[M+Na]+220.20830932474
AllCCS[M+H]+213.032859911
AllCCS[M+H-H2O]+211.232859911
AllCCS[M+NH4]+214.532859911
AllCCS[M+Na]+215.032859911
AllCCS[M-H]-211.432859911
AllCCS[M+Na-2H]-212.532859911
AllCCS[M+HCOO]-213.832859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
HalofantrineCCCCN(CCCC)CCC(O)C1=C2C=CC(=CC2=C2C=C(Cl)C=C(Cl)C2=C1)C(F)(F)F3762.2Standard polar33892256
HalofantrineCCCCN(CCCC)CCC(O)C1=C2C=CC(=CC2=C2C=C(Cl)C=C(Cl)C2=C1)C(F)(F)F3218.1Standard non polar33892256
HalofantrineCCCCN(CCCC)CCC(O)C1=C2C=CC(=CC2=C2C=C(Cl)C=C(Cl)C2=C1)C(F)(F)F3157.2Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Halofantrine,1TMS,isomer #1CCCCN(CCCC)CCC(O[Si](C)(C)C)C1=CC2=C(Cl)C=C(Cl)C=C2C2=CC(C(F)(F)F)=CC=C123055.4Semi standard non polar33892256
Halofantrine,1TBDMS,isomer #1CCCCN(CCCC)CCC(O[Si](C)(C)C(C)(C)C)C1=CC2=C(Cl)C=C(Cl)C=C2C2=CC(C(F)(F)F)=CC=C123276.2Semi standard non polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Halofantrine GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-4908300000-fda0bab8f57ca3a07e802017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Halofantrine GC-MS (1 TMS) - 70eV, Positivesplash10-014i-6300920000-cec8c95eb66963cbe2152017-10-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Halofantrine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Halofantrine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Halofantrine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Halofantrine GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-04Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Halofantrine 10V, Positive-QTOFsplash10-0f89-0001960000-6de4854d3e09f97f38e82016-08-02Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Halofantrine 20V, Positive-QTOFsplash10-0k9x-5906620000-1bd03c8b89b4e08b59a82016-08-02Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Halofantrine 40V, Positive-QTOFsplash10-0a4l-9214100000-762ef2ced883607d0dbb2016-08-02Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Halofantrine 10V, Negative-QTOFsplash10-0002-0000900000-be08a4af62726ab4a2752016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Halofantrine 20V, Negative-QTOFsplash10-002b-0603900000-9b2c085d0f8792872f2e2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Halofantrine 40V, Negative-QTOFsplash10-00b9-9703100000-e44bd620e4350dd3fb8a2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Halofantrine 10V, Positive-QTOFsplash10-0udi-0101090000-d48d790575986c9cda2f2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Halofantrine 20V, Positive-QTOFsplash10-0uk9-0107930000-d721c8f598515e938db72021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Halofantrine 40V, Positive-QTOFsplash10-0w2a-9608100000-51ab02c084d77ef25ac92021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Halofantrine 10V, Negative-QTOFsplash10-0002-0000900000-24430f93d0a912beb13b2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Halofantrine 20V, Negative-QTOFsplash10-0002-0201900000-509c10191484c06e55aa2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Halofantrine 40V, Negative-QTOFsplash10-03fr-1209200000-92e844f4cbc22f33c3492021-10-11Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01218 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01218 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01218
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID34303
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkHalofantrine
METLIN IDNot Available
PubChem CompoundNot Available
PDB IDNot Available
ChEBI IDNot Available
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
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 ]
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.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular weight:
57108.065
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 ]
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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular weight:
55824.275
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 ]
General function:
Involved in ion channel activity
Specific function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular weight:
126653.5
References
  1. Tie H, Walker BD, Singleton CB, Valenzuela SM, Bursill JA, Wyse KR, Breit SN, Campbell TJ: Inhibition of HERG potassium channels by the antimalarial agent halofantrine. Br J Pharmacol. 2000 Aug;130(8):1967-75. [PubMed:10952689 ]
  2. Mbai M, Rajamani S, January CT: The anti-malarial drug halofantrine and its metabolite N-desbutylhalofantrine block HERG potassium channels. Cardiovasc Res. 2002 Sep;55(4):799-805. [PubMed:12176129 ]