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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:50 UTC
Update Date2022-03-07 02:51:43 UTC
HMDB IDHMDB0014746
Secondary Accession Numbers
  • HMDB14746
Metabolite Identification
Common NameChloroquine
DescriptionChloroquine is only found in individuals that have used or taken this drug. It is a prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. [PubChem]The mechanism of plasmodicidal action of chloroquine is not completely certain. Like other quinoline derivatives, it is thought to inhibit heme polymerase activity. This results in accumulation of free heme, which is toxic to the parasites. nside red blood cells, the malarial parasite must degrade hemoglobin to acquire essential amino acids, which the parasite requires to construct its own protein and for energy metabolism. Digestion is carried out in a vacuole of the parasite cell.During this process, the parasite produces the toxic and soluble molecule heme. The heme moiety consists of a porphyrin ring called Fe(II)-protoporphyrin IX (FP). To avoid destruction by this molecule, the parasite biocrystallizes heme to form hemozoin, a non-toxic molecule. Hemozoin collects in the digestive vacuole as insoluble crystals.Chloroquine enters the red blood cell, inhabiting parasite cell, and digestive vacuole by simple diffusion. Chloroquine then becomes protonated (to CQ2+), as the digestive vacuole is known to be acidic (pH 4.7); chloroquine then cannot leave by diffusion. Chloroquine caps hemozoin molecules to prevent further biocrystallization of heme, thus leading to heme buildup. Chloroquine binds to heme (or FP) to form what is known as the FP-Chloroquine complex; this complex is highly toxic to the cell and disrupts membrane function. Action of the toxic FP-Chloroquine and FP results in cell lysis and ultimately parasite cell autodigestion. In essence, the parasite cell drowns in its own metabolic products.
Structure
Data?1582753216
Synonyms
ValueSource
AralenChEBI
ArtrichinChEBI
BemaphateChEBI
CapquinChEBI
ChlorochinChEBI
ChloroquinumChEBI
CloroquinaChEBI
N(4)-(7-Chloro-4-quinolinyl)-N(1),N(1)-diethyl-1,4-pentanediamineChEBI
Nivaquine bChEBI
ResoquineChEBI
ReumachlorChEBI
SanoquinChEBI
Bemaphic acidGenerator
ChloraquineHMDB
ChlorochineHMDB
ChloroquinaHMDB
ChloroquiniumHMDB
ChlorquinHMDB
ClorochinaHMDB
ChingaminHMDB
ArechineHMDB
KhingaminHMDB
Sulphate, chloroquineHMDB
ArequinHMDB
Chloroquine sulfateHMDB
Chloroquine sulphateHMDB
NivaquineHMDB
Sulfate, chloroquineHMDB
Chemical FormulaC18H26ClN3
Average Molecular Weight319.872
Monoisotopic Molecular Weight319.181525554
IUPAC Name7-chloro-N-[5-(diethylamino)pentan-2-yl]quinolin-4-amine
Traditional Name7-chloro-N-[5-(diethylamino)pentan-2-yl]quinolin-4-amine
CAS Registry Number54-05-7
SMILES
CCN(CC)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1
InChI Identifier
InChI=1S/C18H26ClN3/c1-4-22(5-2)12-6-7-14(3)21-17-10-11-20-18-13-15(19)8-9-16(17)18/h8-11,13-14H,4-7,12H2,1-3H3,(H,20,21)
InChI KeyWHTVZRBIWZFKQO-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as 4-aminoquinolines. These are organic compounds containing an amino group attached to the 4-position of a quinoline ring system.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassAminoquinolines and derivatives
Direct Parent4-aminoquinolines
Alternative Parents
Substituents
  • 4-aminoquinoline
  • Haloquinoline
  • Chloroquinoline
  • Aminopyridine
  • Secondary aliphatic/aromatic amine
  • Aryl chloride
  • Aryl halide
  • Pyridine
  • Benzenoid
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Secondary amine
  • Amine
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effectNot Available
Disposition
ProcessNot Available
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point289 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.018 g/LNot Available
LogP4.3Not Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M+H]+CBM176.830932474
[M+H]+Not Available175.554http://allccs.zhulab.cn/database/detail?ID=AllCCS00000968
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.018 g/LALOGPS
logP5.28ALOGPS
logP3.93ChemAxon
logS-4.3ALOGPS
pKa (Strongest Basic)10.32ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area28.16 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity96.42 m³·mol⁻¹ChemAxon
Polarizability37.29 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DeepCCS[M+H]+180.48430932474
DeepCCS[M-H]-178.12630932474
DeepCCS[M-2H]-211.01230932474
DeepCCS[M+Na]+186.57730932474
AllCCS[M+H]+178.332859911
AllCCS[M+H-H2O]+175.332859911
AllCCS[M+NH4]+181.132859911
AllCCS[M+Na]+181.932859911
AllCCS[M-H]-181.032859911
AllCCS[M+Na-2H]-181.432859911
AllCCS[M+HCOO]-182.132859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
ChloroquineCCN(CC)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C13479.3Standard polar33892256
ChloroquineCCN(CC)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C12630.9Standard non polar33892256
ChloroquineCCN(CC)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C12631.6Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Chloroquine,1TMS,isomer #1CCN(CC)CCCC(C)N(C1=CC=NC2=CC(Cl)=CC=C12)[Si](C)(C)C2501.8Semi standard non polar33892256
Chloroquine,1TMS,isomer #1CCN(CC)CCCC(C)N(C1=CC=NC2=CC(Cl)=CC=C12)[Si](C)(C)C2556.7Standard non polar33892256
Chloroquine,1TMS,isomer #1CCN(CC)CCCC(C)N(C1=CC=NC2=CC(Cl)=CC=C12)[Si](C)(C)C3066.3Standard polar33892256
Chloroquine,1TBDMS,isomer #1CCN(CC)CCCC(C)N(C1=CC=NC2=CC(Cl)=CC=C12)[Si](C)(C)C(C)(C)C2690.1Semi standard non polar33892256
Chloroquine,1TBDMS,isomer #1CCN(CC)CCCC(C)N(C1=CC=NC2=CC(Cl)=CC=C12)[Si](C)(C)C(C)(C)C2787.2Standard non polar33892256
Chloroquine,1TBDMS,isomer #1CCN(CC)CCCC(C)N(C1=CC=NC2=CC(Cl)=CC=C12)[Si](C)(C)C(C)(C)C3150.9Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental GC-MSGC-MS Spectrum - Chloroquine CI-B (Non-derivatized)splash10-00di-0009000000-d54119d64cfc341cee7d2017-09-12HMDB team, MONA, MassBankView Spectrum
Experimental GC-MSGC-MS Spectrum - Chloroquine CI-B (Non-derivatized)splash10-00di-0009000000-d54119d64cfc341cee7d2018-05-18HMDB team, MONA, MassBankView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Chloroquine GC-MS (Non-derivatized) - 70eV, Positivesplash10-0pbi-9242000000-6cd79ce1c8a9ada4550d2017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Chloroquine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
MSMass Spectrum (Electron Ionization)splash10-000i-9320000000-2663c398ede2e502ca342014-09-20Not AvailableView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Chloroquine 40V, Positive-QTOFsplash10-002p-8920000000-552012cb889bf65320d82021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Chloroquine 20V, Positive-QTOFsplash10-0002-0391000000-7360fd3b6728bd6574b82021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Chloroquine 10V, Positive-QTOFsplash10-00di-0029000000-3ea9f3105801d7abf0802021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Chloroquine 10V, Positive-QTOFsplash10-00di-0119000000-8f9d4513bf5993f3c9c42016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Chloroquine 20V, Positive-QTOFsplash10-00dl-3957000000-e533e26da609c9329dae2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Chloroquine 40V, Positive-QTOFsplash10-00bc-9530000000-646244109f4c47e0c2a62016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Chloroquine 10V, Negative-QTOFsplash10-014i-0009000000-d45e56a4f82a2d58657d2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Chloroquine 20V, Negative-QTOFsplash10-014i-1229000000-09769326d92e55dd78aa2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Chloroquine 40V, Negative-QTOFsplash10-00fu-9630000000-f2986e805921cc8d3a372016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Chloroquine 10V, Positive-QTOFsplash10-00di-0049000000-7e55e664b21e89ddbe442021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Chloroquine 20V, Positive-QTOFsplash10-00dj-0198000000-64a0ed0e3e428bf65cbb2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Chloroquine 40V, Positive-QTOFsplash10-004r-6950000000-75bff8c32e9dcca35dbf2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Chloroquine 10V, Negative-QTOFsplash10-014i-0009000000-b550e787bd639403cc762021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Chloroquine 20V, Negative-QTOFsplash10-014i-0109000000-3494d09f71ff43a3ce732021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Chloroquine 40V, Negative-QTOFsplash10-004i-2910000000-efba909b8046e2bf2c672021-10-11Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00608 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00608 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00608
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2618
KEGG Compound IDC07625
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkChloroquine
METLIN IDNot Available
PubChem Compound2719
PDB IDNot Available
ChEBI ID3638
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 glutathione transferase activity
Specific function:
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Gene Name:
GSTA2
Uniprot ID:
P09210
Molecular weight:
25663.675
References
  1. 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 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.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular weight:
58164.815
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 tumor necrosis factor receptor binding
Specific function:
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation
Gene Name:
TNF
Uniprot ID:
P01375
Molecular weight:
25644.1
References
  1. Jang CH, Choi JH, Byun MS, Jue DM: Chloroquine inhibits production of TNF-alpha, IL-1beta and IL-6 from lipopolysaccharide-stimulated human monocytes/macrophages by different modes. Rheumatology (Oxford). 2006 Jun;45(6):703-10. Epub 2006 Jan 17. [PubMed:16418198 ]
  2. Rachmilewitz D, Karmeli F, Shteingart S, Lee J, Takabayashi K, Raz E: Immunostimulatory oligonucleotides inhibit colonic proinflammatory cytokine production in ulcerative colitis. Inflamm Bowel Dis. 2006 May;12(5):339-45. [PubMed:16670522 ]
  3. Wozniacka A, Lesiak A, Narbutt J, McCauliffe DP, Sysa-Jedrzejowska A: Chloroquine treatment influences proinflammatory cytokine levels in systemic lupus erythematosus patients. Lupus. 2006;15(5):268-75. [PubMed:16761500 ]
  4. Lim EJ, Lee SH, Lee JG, Chin BR, Bae YS, Kim JR, Lee CH, Baek SH: Activation of toll-like receptor-9 induces matrix metalloproteinase-9 expression through Akt and tumor necrosis factor-alpha signaling. FEBS Lett. 2006 Aug 7;580(18):4533-8. Epub 2006 Jul 17. [PubMed:16870179 ]
  5. Dias-Melicio LA, Calvi SA, Bordon AP, Golim MA, Peracoli MT, Soares AM: Chloroquine is therapeutic in murine experimental model of paracoccidioidomycosis. FEMS Immunol Med Microbiol. 2007 Jun;50(1):133-43. Epub 2007 Apr 23. [PubMed:17456179 ]
General function:
Involved in protein binding
Specific function:
Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific of microorganisms. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response
Gene Name:
TLR9
Uniprot ID:
Q9NR96
Molecular weight:
115858.7
References
  1. Trevani AS, Chorny A, Salamone G, Vermeulen M, Gamberale R, Schettini J, Raiden S, Geffner J: Bacterial DNA activates human neutrophils by a CpG-independent pathway. Eur J Immunol. 2003 Nov;33(11):3164-74. [PubMed:14579285 ]
  2. Rutz M, Metzger J, Gellert T, Luppa P, Lipford GB, Wagner H, Bauer S: Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner. Eur J Immunol. 2004 Sep;34(9):2541-50. [PubMed:15307186 ]
  3. Lenert P: Inhibitory oligodeoxynucleotides - therapeutic promise for systemic autoimmune diseases? Clin Exp Immunol. 2005 Apr;140(1):1-10. [PubMed:15762869 ]
  4. Huang LY, Ishii KJ, Akira S, Aliberti J, Golding B: Th1-like cytokine induction by heat-killed Brucella abortus is dependent on triggering of TLR9. J Immunol. 2005 Sep 15;175(6):3964-70. [PubMed:16148144 ]
  5. Merrell MA, Ilvesaro JM, Lehtonen N, Sorsa T, Gehrs B, Rosenthal E, Chen D, Shackley B, Harris KW, Selander KS: Toll-like receptor 9 agonists promote cellular invasion by increasing matrix metalloproteinase activity. Mol Cancer Res. 2006 Jul;4(7):437-47. [PubMed:16849519 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [PubMed:11602674 ]