ContaminantDB: Chloroquine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (11)XML

Record Information

Version

1.0

Creation Date

2009-07-05 03:00:49 UTC

Update Date

2026-05-14 16:43:53 UTC

Accession Number

CHEM002087

Identification

Common Name

Chloroquine

Class

Small Molecule

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.

Contaminant Sources

HMDB Contaminants - Urine
IARC Carcinogens Group 3
STOFF IDENT Compounds
T3DB toxins

Contaminant Type

Amebicide
Amine
Antimalarial
Antirheumatic Agent
Drug
Human Neurotoxin
Metabolite
Organic Compound
Organochloride
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
Aralen	ChEBI
Artrichin	ChEBI
Bemaphate	ChEBI
Capquin	ChEBI
Chlorochin	ChEBI
Chloroquinum	ChEBI
Cloroquina	ChEBI
N(4)-(7-Chloro-4-quinolinyl)-N(1),N(1)-diethyl-1,4-pentanediamine	ChEBI
Nivaquine b	ChEBI
Resoquine	ChEBI
Reumachlor	ChEBI
Sanoquin	ChEBI
Bemaphic acid	Generator
Chloraquine	HMDB
Chlorochine	HMDB
Chloroquina	HMDB
Chloroquinium	HMDB
Chlorquin	HMDB
Clorochina	HMDB
Chingamin	HMDB
Arechine	HMDB
Khingamin	HMDB
Sulphate, chloroquine	HMDB
Arequin	HMDB
Chloroquine sulfate	HMDB
Chloroquine sulphate	HMDB
Nivaquine	HMDB
Sulfate, chloroquine	HMDB

Chemical Formula

C₁₈H₂₆ClN₃

Average Molecular Mass

319.872 g/mol

Monoisotopic Mass

319.182 g/mol

CAS Registry Number

54-05-7

IUPAC Name

7-chloro-N-[5-(diethylamino)pentan-2-yl]quinolin-4-amine

Traditional Name

7-chloro-N-[5-(diethylamino)pentan-2-yl]quinolin-4-amine

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

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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Quinolines and derivatives

Sub Class

Aminoquinolines and derivatives

Direct Parent

4-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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

tertiary amino compound (CHEBI:3638 )
organochlorine compound (CHEBI:3638 )
secondary amino compound (CHEBI:3638 )
aminoquinoline (CHEBI:3638 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White to slightly yellow, crystalline powder (2).

Experimental Properties

Property	Value
Melting Point	289°C
Boiling Point	Not Available
Solubility	10.6 mg/L

Predicted Properties

Property	Value	Source
Water Solubility	0.018 g/L	ALOGPS
logP	5.28	ALOGPS
logP	3.93	ChemAxon
logS	-4.3	ALOGPS
pKa (Strongest Basic)	10.32	ChemAxon
Physiological Charge	2	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	28.16 Å²	ChemAxon
Rotatable Bond Count	8	ChemAxon
Refractivity	96.42 m³·mol⁻¹	ChemAxon
Polarizability	37.29 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
GC-MS	GC-MS Spectrum - CI-B (Non-derivatized)	splash10-00di-0009000000-d54119d64cfc341cee7d	Spectrum
GC-MS	GC-MS Spectrum - CI-B (Non-derivatized)	splash10-00di-0009000000-d54119d64cfc341cee7d	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0pbi-9242000000-6cd79ce1c8a9ada4550d	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-002p-8920000000-552012cb889bf65320d8	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-0002-0391000000-7360fd3b6728bd6574b8	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-00di-0029000000-3ea9f3105801d7abf080	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00di-0119000000-8f9d4513bf5993f3c9c4	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00dl-3957000000-e533e26da609c9329dae	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00bc-9530000000-646244109f4c47e0c2a6	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-014i-0009000000-d45e56a4f82a2d58657d	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-014i-1229000000-09769326d92e55dd78aa	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00fu-9630000000-f2986e805921cc8d3a37	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00di-0049000000-7e55e664b21e89ddbe44	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00dj-0198000000-64a0ed0e3e428bf65cbb	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-004r-6950000000-75bff8c32e9dcca35dbf	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-014i-0009000000-b550e787bd639403cc76	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-014i-0109000000-3494d09f71ff43a3ce73	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-004i-2910000000-efba909b8046e2bf2c67	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-000i-9320000000-2663c398ede2e502ca34	Spectrum

Toxicity Profile

Route of Exposure

Inhalation Completely absorbed from gastrointestinal tract

Mechanism of Toxicity

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.

Metabolism

Completely absorbed from gastrointestinal tract. Chloroquine is partially metabolized; the major metabolite is desethylchloroquine. Desethylchloroquine also has antiplasmodial activity, but is slightly less active than chloroquine. Bisdesethylchloroquine, which is a carboxylic acid derivative, and several other unidentified metabolites are also formed in small amounts (3). Route of Elimination: Excretion of chloroquine is quite slow, but is increased by acidification of the urine. Half Life: 1-2 months

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

3, not classifiable as to its carcinogenicity to humans. (4)

Uses/Sources

For the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum, Second-line agent in treatment of Rheumatoid Arthritis (1).

Minimum Risk Level

Not Available

Health Effects

Possible heath effects include an irreversible retinal damage, visual disturbances, nyctalopia; scotomatous vision with field defects of paracentral, pericentral ring types, and typically temporal scotomas, nerve type deafness; tinnitus, reduced hearing in patients with preexisting auditory damage. Other effects include pleomorphic skin eruptions, skeletal muscle myopathy, hypotension, electrocardiographic change as well as neuropsychiatric changes including psychosis, delirium, personality changes and depression (RxList, A308).

Symptoms

Convulsive seizures. Mild and transient headache.

Treatment

Treatment is symptomatic and must be prompt with immediate evacuation of the stomach by emesis (at home, before transportation to the hospital) or gastric lavage until the stomach is completely emptied. If finely powdered, activated charcoal is introduced by stomach tube, after lavage, and within 30 minutes after ingestion of the antimalarial, it may inhibit further intestinal absorption of the drug. To be effective, the dose of activated charcoal should be at least five times the estimated dose of chloroquine ingested. Convulsions, if present, should be controlled before attempting gastric lavage. (5)

Concentrations

Not Available

External Links

DrugBank ID

DB00608

HMDB ID

HMDB0014746

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID