Record Information
Version3.6
Creation Date2012-09-06 15:16:50 UTC
Update Date2013-02-09 00:32:14 UTC
HMDB IDHMDB14746
Secondary Accession NumbersNone
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
Thumb
Synonyms
  1. Chloraquine
  2. Chlorochine
  3. Chloroquina
  4. Chloroquinium
  5. Chlorquin
  6. Clorochina
Chemical FormulaC18H26ClN3
Average Molecular Weight319.872
Monoisotopic Molecular Weight319.181525554
IUPAC Name{4-[(7-chloroquinolin-4-yl)amino]pentyl}diethylamine
Traditional IUPAC Namechloroquine
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
KingdomOrganic Compounds
Super ClassAromatic Heteropolycyclic Compounds
ClassQuinolines and Derivatives
Sub ClassAminoquinolines and Derivatives
Other Descriptors
  • Aromatic Heteropolycyclic Compounds
  • quinoline alkaloid(ChEBI)
Substituents
  • Aminopyridine
  • Aryl Chloride
  • Chlorobenzene
  • Organochloride
  • Polyamine
  • Pyridine
  • Tertiary Aliphatic Amine (Trialkylamine)
Direct ParentAminoquinolines and Derivatives
Ontology
StatusExpected and Not Quantified
Origin
  • Drug
Biofunction
  • Amebicides
  • Antimalarials
  • Antirheumatic Agents
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Extracellular
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point289 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.75e-02 g/LNot Available
LogP4.3Not Available
Predicted 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 area28.16ChemAxon
rotatable bond count8ChemAxon
refractivity96.42ChemAxon
polarizability37.29ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReference
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00608
  • Not Applicable
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00608
  • Not Applicable
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00608
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2618
KEGG Compound IDC07625
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkChloroquine
NuGOwiki LinkHMDB14746
Metagene LinkHMDB14746
METLIN IDNot Available
PubChem Compound2719
PDB IDNot Available
ChEBI ID3638
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

Gene Name:
GSTA2
Uniprot ID:
P09210
Gene Name:
CYP3A4
Uniprot ID:
P08684
Gene Name:
CYP2D6
Uniprot ID:
P10635
Gene Name:
CYP3A5
Uniprot ID:
P20815
Gene Name:
CYP1A1
Uniprot ID:
P04798
Gene Name:
CYP2C8
Uniprot ID:
P10632
Gene Name:
TNF
Uniprot ID:
P01375
Gene Name:
TLR9
Uniprot ID:
Q9NR96

Transporters

Gene Name:
ABCB1
Uniprot ID:
P08183