Human Metabolome Database Version 3.5

Showing metabocard for Chloroquine (HMDB14746)

Record Information
Version 3.5
Creation Date 2012-09-06 09:16:50 -0600
Update Date 2013-02-08 17:32:14 -0700
HMDB ID HMDB14746
Secondary Accession Numbers None
Metabolite Identification
Common Name Chloroquine
Description Chloroquine 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
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Synonyms
  1. Chloraquine
  2. Chlorochine
  3. Chloroquina
  4. Chloroquinium
  5. Chlorquin
  6. Clorochina
Chemical Formula C18H26ClN3
Average Molecular Weight 319.872
Monoisotopic Molecular Weight 319.181525554
IUPAC Name {4-[(7-chloroquinolin-4-yl)amino]pentyl}diethylamine
Traditional IUPAC Name chloroquine
CAS Registry Number 54-05-7
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 Key WHTVZRBIWZFKQO-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Aromatic Heteropolycyclic Compounds
Class Quinolines and Derivatives
Sub Class Aminoquinolines and Derivatives
Other Descriptors
  • Aromatic Heteropolycyclic Compounds
  • quinoline alkaloid(ChEBI)
Substituents
  • Aminopyridine
  • Aryl Chloride
  • Chlorobenzene
  • Organochloride
  • Polyamine
  • Pyridine
  • Tertiary Aliphatic Amine (Trialkylamine)
Direct Parent Aminoquinolines and Derivatives
Ontology
Status Expected and Not Quantified
Origin
  • Drug
Biofunction
  • Amebicides
  • Antimalarials
  • Antirheumatic Agents
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Extracellular
  • Membrane
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 289 °C Not Available
Boiling Point Not Available Not Available
Water Solubility 1.75e-02 g/L Not Available
LogP 4.3 Not Available
Predicted Properties
Property Value Source
LogP 5.28 ALOGPS
LogP 3.93 ChemAxon
LogS -4.26 ALOGPS
pKa (strongest basic) 10.32 ChemAxon
Hydrogen Acceptor Count 3 ChemAxon
Hydrogen Donor Count 1 ChemAxon
Polar Surface Area 28.16 A2 ChemAxon
Rotatable Bond Count 8 ChemAxon
Refractivity 96.42 ChemAxon
Polarizability 37.29 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge 2 ChemAxon
Spectra
Not Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue Location Not Available
Pathways Not Available
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Expected but not Quantified
Not Applicable Not Available Not Available Taking drug identified by DrugBank entry DB00608
  • Not Applicable
Urine Expected but not Quantified
Not Applicable Not Available Not Available Taking drug identified by DrugBank entry DB00608
  • Not Applicable
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease References None
Associated OMIM IDs None
DrugBank ID DB00608 Link_out
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 2618 Link_out
KEGG Compound ID C07625 Link_out
BioCyc ID Not Available
BiGG ID Not Available
Wikipedia Link Chloroquine Link_out
NuGOwiki Link HMDB14746 Link_out
Metagene Link HMDB14746 Link_out
METLIN ID Not Available
PubChem Compound 2719 Link_out
PDB ID Not Available
ChEBI ID 3638 Link_out
References
Synthesis Reference Not Available
Material Safety Data Sheet (MSDS) Not Available
General References Not Available

Enzymes
Name: Glutathione S-transferase A2
Reactions: Not Available
Gene Name: GSTA2
Uniprot ID: P09210 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Cytochrome P450 3A4
Reactions: Not Available
Gene Name: CYP3A4
Uniprot ID: P08684 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Cytochrome P450 2D6
Reactions: Not Available
Gene Name: CYP2D6
Uniprot ID: P10635 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Cytochrome P450 3A5
Reactions: Not Available
Gene Name: CYP3A5
Uniprot ID: P20815 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Cytochrome P450 1A1
Reactions: Not Available
Gene Name: CYP1A1
Uniprot ID: P04798 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Cytochrome P450 2C8
Reactions: Not Available
Gene Name: CYP2C8
Uniprot ID: P10632 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Tumor necrosis factor
Reactions: Not Available
Gene Name: TNF
Uniprot ID: P01375 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Toll-like receptor 9
Reactions: Not Available
Gene Name: TLR9
Uniprot ID: Q9NR96 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Transporters
Name: Multidrug resistance protein 1
Reactions: Not Available
Gene Name: ABCB1
Uniprot ID: P08183 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA