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Identification
Name Chloroquine
Accession Number DB00608 (APRD00468)
Type small molecule
Groups approved
Description

The 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]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Chloraquine
Chlorochine
Chloroquina
Chloroquinium
Chlorquin
Clorochina
Salts
  • Chloroquine Phosphate
Brand names
Name Company
Amokin
Aralen
Arechin
Arthrochin
Artrichin
Avlochlor
Avloclor
Bemaco
Bemaphate
Bemasulph
Benaquin
Bipiquin
Capquin
Chemochin
Chingamin
Chlorochin
Cidanchin
Cocartrit
Dawaquin
Delagil
Dichinalex
Elestol
Gontochin
Heliopar
Imagon
Iroquine
Klorokin
Lapaquin
Malaquin
Malaren
Malarex
Mesylith
Neochin
Nivachine
Nivaquine
Nivaquine B
Quinachlor
Quinagamin
Quinagamine
Quinercyl
Quingamine
Quinilon
Quinoscan
Resochen
Resochin
Resoquina
Resoquine
Reumachlor
Reumaquin
Roquine
Sanoquin
Silbesan
Siragan
Solprina
Sopaquin
Tanakan
Tresochin
Trochin
First Prev Next Last
Brand mixtures Not Available
Categories
  • Antirheumatic Agents
  • Antimalarials
  • Amebicides
CAS number 54-05-7
Weight Average: 319.872
Monoisotopic: 319.181525554
Chemical Formula C18H26ClN3
InChI Key InChIKey=WHTVZRBIWZFKQO-UHFFFAOYSA-N
InChI
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)
Plain Text
IUPAC Name
{4-[(7-chloroquinolin-4-yl)amino]pentyl}diethylamine
SMILES
CCN(CC)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1
Plain Text
Mass Spec show (8.47 KB)
Taxonomy
Kingdom Organic
Classes
  • Aminoquinolines and Derivatives
  • (Iso)quinolines and Derivatives
Substructures
  • Aliphatic and Aryl Amines
  • Pyridines and Derivatives
  • Benzene and Derivatives
  • Aryl Halides
  • Aminoquinolines and Derivatives
  • Halobenzenes
  • Aminopyridines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • (Iso)quinolines and Derivatives
Pharmacology
Indication 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
Pharmacodynamics Chloroquine is the prototype anti malarial drug, most widely used to treat all types of malaria except for disease caused by chloroquine resistant Plasmodium falciparum. It is highly effective against erythrocytic forms of Plasmodium vivax, Plasmodium ovale and Plasmodium malariae, sensitive strains of Plasmodium falciparum and gametocytes of Plasmodium vivax. Being alkaline, the drug reaches high concentration within the food vacuoles of the parasite and raises its pH. It is found to induce rapid clumping of the pigment. Chloroquine inhibits the parasitic enzyme heme polymerase that converts the toxic heme into non-toxic hemazoin, thereby resulting in the accumulation of toxic heme within the parasite. It may also interfere with the biosynthesis of nucleic acids.
Mechanism of action 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.
Absorption Completely absorbed from gastrointestinal tract
Volume of distribution Not Available
Protein binding ~55% of the drug in the plasma is bound to nondiffusible plasma constituents
Metabolism
Hepatic (partially)
Route of elimination Excretion of chloroquine is quite slow, but is increased by acidification of the urine.
Half life 1-2 months
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Plasmodium
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
  • Impax laboratories inc
  • Ipca laboratories ltd
  • Md pharmaceutical inc
  • Purepac pharmaceutical co
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • West ward pharmaceutical corp
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Aralen 500 mg tablet 7.85 USD tablet
Aralen phosphate 500 mg tablet 7.78 USD tablet
Chloroquine ph 500 mg tablet 5.64 USD tablet
Chloroquine Phosphate 500 mg tablet 5.42 USD tablet
Chloroquine phosphate powdr 4.29 USD g
Plaquenil 200 mg tablet 3.14 USD tablet
Chloroquine Phosphate 250 mg tablet 2.57 USD tablet
Chloroquine ph 250 mg tablet 2.49 USD tablet
Novo-Chloroquine 250 mg Tablet 0.35 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 289 dec °C PhysProp
water solubility 10.6 mg/L Not Available
logP 4.63 HANSCH,C ET AL. (1995)
pKa 10.1 SANGSTER (1994)
Predicted Properties
Property Value Source
water solubility 1.75e-02 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 ChemAxon
rotatable bond count 8 ChemAxon
refractivity 96.42 ChemAxon
polarizability 37.29 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D02366 Link_out
KEGG Compound C07625 Link_out
PubChem Compound 2719 Link_out
PubChem Substance 46506925 Link_out
ChemSpider 2618 Link_out
BindingDB 22985 Link_out
ChEBI 3638 Link_out
ChEMBL 3638 Link_out
Therapeutic Targets Database DAP001357 Link_out
PharmGKB PA448948 Link_out
HET CLQ Link_out
Drug Product Database 21261 Link_out
RxList http://www.rxlist.com/cgi/generic2/hquine2.htm Link_out
Drugs.com http://www.drugs.com/cdi/chloroquine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Chloroquine Link_out
ATC Codes
  • P01BA01
  • P01BA02
AHFS Codes
  • 08:30.08
PDB Entries
FDA label show (153 KB)
MSDS show (74.9 KB)
Interactions
Drug Interactions
Drug Interaction
Aluminium The antiacid decreases the absorption of chloroquine
Artemether Chloroquine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
Atomoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Attapulgite The antiacid decreases the absorption of chloroquine
Calcium The antiacid decreases the absorption of chloroquine
Cyclosporine Chloroquine may increase the therapeutic and adverse effects of cyclosporine.
Dihydroxyaluminium The antiacid decreases the absorption of chloroquine
Kaolin The antiacid decreases the absorption of chloroquine
Lumefantrine Chloroquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
Magnesium The antiacid decreases the absorption of chloroquine
Magnesium oxide The antiacid decreases the absorption of chloroquine
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Praziquantel Markedly lower praziquantel levels
Tamoxifen Chloroquine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Tamsulosin Chloroquine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Chloroquine is initiated, discontinued, or dose changed.
Telithromycin Telithromycin may reduce clearance of Chloroquine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Chloroquine if Telithromycin is initiated, discontinued or dose changed.
Terbinafine Terbinafine may reduce the metabolism and clearance of Chloroquine. Consider alternate therapy or monitor for therapeutic/adverse effects of Chloroquine if Terbinafine is initiated, discontinued or dose changed.
Thioridazine Increased risk of cardiotoxicity and arrhythmias
Tramadol Chloroquine may decrease the effect of Tramadol by decreasing active metabolite production.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of chloroquine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of chloroquine if voriconazole is initiated, discontinued or dose changed.
Food Interactions
  • Take with food to reduce irritation and increase bioavailability.
Targets

1. Ferriprotoporphyrin IX

Pharmacological action: yes
Actions: antagonist

References:
  1. Fitch CD: Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci. 2004 Mar 5;74(16):1957-72. Pubmed
  2. Dorn A, Vippagunta SR, Matile H, Jaquet C, Vennerstrom JL, Ridley RG: An assessment of drug-haematin binding as a mechanism for inhibition of haematin polymerisation by quinoline antimalarials. Biochem Pharmacol. 1998 Mar 15;55(6):727-36. Pubmed
  3. Stoller TJ, Shields D: The propeptide of preprosomatostatin mediates intracellular transport and secretion of alpha-globin from mammalian cells. J Cell Biol. 1989 May;108(5):1647-55. Pubmed
  4. Mockenhaupt FP, May J, Bergqvist Y, Meyer CG, Falusi AG, Bienzle U: Evidence for a reduced effect of chloroquine against Plasmodium falciparum in alpha-thalassaemic children. Trop Med Int Health. 2001 Feb;6(2):102-7. Pubmed

2. Glutathione S-transferase A2

Pharmacological action: unknown

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles

Organism class: human
UniProt ID: P09210 Link_out
Gene: GSTA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Tumor necrosis factor

Pharmacological action: unknown

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

Organism class: human
UniProt ID: P01375 Link_out
Gene: TNF Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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

4. Toll-like receptor 9

Pharmacological action: unknown

Participates in the innate immune response to microbial agents. Detects the unmethylated cytidine-phosphate-guanosine (CpG) motifs present in bacterial DNA. Acts via MyD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response

Organism class: human
UniProt ID: Q9NR96 Link_out
Gene: TLR9 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Lenert P: Inhibitory oligodeoxynucleotides – therapeutic promise for systemic autoimmune diseases? Clin Exp Immunol. 2005 Apr;140(1):1-10. Pubmed
  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
  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
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

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. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2D6

Actions: substrate, inhibitor

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

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 1A1

Actions: substrate

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

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C8

Actions: substrate

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)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 3A5

Actions: substrate

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

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19