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Identification
NameQuinacrine
Accession NumberDB01103  (APRD00317)
TypeSmall Molecule
GroupsApproved
Description

An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
2-Methoxy-6-chloro-9-diethylaminopentylaminoacridineNot AvailableNot Available
3-chloro-7-Methoxy-9-(1-methyl-4-diethylaminobutylamino)acridineNot AvailableNot Available
6-chloro-9-((4-(Diethylamino)-1-methylbutyl)amino)-2-methoxyacridineNot AvailableNot Available
MepacrineNot AvailableINN
N(4)-(6-chloro-2-Methoxy-9-acridinyl)-N(1),N(1)-diethyl-1,4-pentanediamineNot AvailableNot Available
QuinacrineNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
AtabrineNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Quinacrine Dihydrochloride
Thumb
  • InChI Key: UDKVBVICMUEIKS-UHFFFAOYNA-N
  • Monoisotopic Mass: 471.161095782
  • Average Mass: 472.879
DBSALT000420
Categories
CAS number83-89-6
WeightAverage: 399.957
Monoisotopic: 399.207740304
Chemical FormulaC23H30ClN3O
InChI KeyGPKJTRJOBQGKQK-UHFFFAOYSA-N
InChI
InChI=1S/C23H30ClN3O/c1-5-27(6-2)13-7-8-16(3)25-23-19-11-9-17(24)14-22(19)26-21-12-10-18(28-4)15-20(21)23/h9-12,14-16H,5-8,13H2,1-4H3,(H,25,26)
IUPAC Name
6-chloro-N-[5-(diethylamino)pentan-2-yl]-2-methoxyacridin-9-amine
SMILES
CCN(CC)CCCC(C)NC1=C2C=C(OC)C=CC2=NC2=C1C=CC(Cl)=C2
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as acridines. These are organic compounds containing the acridine moiety, a linear tricyclic heterocycle which consists of two benzene rings joined by a pyridine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassBenzoquinolines
Direct ParentAcridines
Alternative Parents
Substituents
  • Acridine
  • Chloroquinoline
  • Hydroxyquinoline
  • Aminoquinoline
  • Anisole
  • Secondary aliphatic/aromatic amine
  • Chlorobenzene
  • Aminopyridine
  • Alkyl aryl ether
  • Benzenoid
  • Pyridine
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Secondary amine
  • Ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of giardiasis and cutaneous leishmaniasis and the management of malignant effusions.
PharmacodynamicsQuinacrine has been used as an antimalarial drug and as an antibiotic. It is used to treat giardiasis, a protozoal infection of the intestinal tract, and certain types of lupus erythematosus, an inflammatory disease that affects the joints, tendons, and other connective tissues and organs. Quinacrine may be injected into the space surrounding the lungs to prevent reoccurrence of pneumothorax. The exact way in which quinacrine works is unknown. It appears to interfere with the parasite's metabolism.
Mechanism of actionThe exact mechanism of antiparasitic action is unknown; however, quinacrine binds to deoxyribonucleic acid (DNA) in vitro by intercalation between adjacent base pairs, inhibiting transcription and translation to ribonucleic acid (RNA). Quinacrine does not appear to localize to the nucleus of Giaridia trophozoites, suggesting that DNA binding may not be the primary mechanism of its antimicrobial action. Fluorescence studies using Giardia suggest that the outer membranes may be involved. Quinacrine inhibits succinate oxidation and interferes with electron transport. In addition, by binding to nucleoproteins, quinacrine suppress the lupus erythematous cell factor and acts as a strong inhibitor of cholinesterase.
AbsorptionAbsorbed rapidly from the gastrointestinal tract following oral administration.
Volume of distributionNot Available
Protein binding80-90%
MetabolismNot Available
Route of eliminationNot Available
Half life5 to 14 days
ClearanceNot Available
ToxicityOral, rat: LD50 = 900 mg/kg; Oral, mouse: LD50 = 1000 mg/kg. Symptoms of overdose include seizures, hypotension, cardiac arrhythmias, and cardiovascular collapse.
Affected organisms
  • Parasitic protozoa and helminths
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9952
Blood Brain Barrier+0.9253
Caco-2 permeable+0.596
P-glycoprotein substrateSubstrate0.8401
P-glycoprotein inhibitor IInhibitor0.7537
P-glycoprotein inhibitor IIInhibitor0.8526
Renal organic cation transporterInhibitor0.6497
CYP450 2C9 substrateNon-substrate0.8442
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.701
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 substrateNon-inhibitor0.9185
CYP450 2D6 substrateInhibitor0.8932
CYP450 2C19 substrateNon-inhibitor0.9025
CYP450 3A4 substrateNon-inhibitor0.9063
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5494
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.8806
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.8888 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.585
hERG inhibition (predictor II)Inhibitor0.8622
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Quinacrine hcl powder8.11USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point248-250 °CNot Available
water solubilitySlightNot Available
logP5.5Not Available
pKa10.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00239 mg/mLALOGPS
logP6.13ALOGPS
logP5.15ChemAxon
logS-5.2ALOGPS
pKa (Strongest Basic)10.33ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.39 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity118.96 m3·mol-1ChemAxon
Polarizability46.32 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US2113357
General Reference
  1. Canete R, Escobedo AA, Gonzalez ME, Almirall P: Randomized clinical study of five days apostrophe therapy with mebendazole compared to quinacrine in the treatment of symptomatic giardiasis in children. World J Gastroenterol. 2006 Oct 21;12(39):6366-70. Pubmed
  2. Toubi E, Kessel A, Rosner I, Rozenbaum M, Paran D, Shoenfeld Y: The reduction of serum B-lymphocyte activating factor levels following quinacrine add-on therapy in systemic lupus erythematosus. Scand J Immunol. 2006 Apr;63(4):299-303. Pubmed
  3. Zipper J, Cole LP, Goldsmith A, Wheeler R, Rivera M: Quinacrine hydrochloride pellets: preliminary data on a nonsurgical method of female sterilization. Int J Gynaecol Obstet. 1980;18(4):275-9. Pubmed
  4. Bhatt RV: Camp laparoscopic sterilization deaths in Gujarat State, India, 1978-1980. Asia Oceania J Obstet Gynaecol. 1991 Dec;17(4):297-301. Pubmed
  5. Peterson HB, Lubell I, DeStefano F, Ory HW: The safety and efficacy of tubal sterilization: an international overview. Int J Gynaecol Obstet. 1983 Apr;21(2):139-44. Pubmed
External Links
ATC CodesP01AX05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (73.8 KB)
Interactions
Drug Interactions
Drug
ChloroquineAminoquinolines (Antimalarial) may decrease the serum concentration of Anthelmintics.
HydroxychloroquineAminoquinolines (Antimalarial) may decrease the serum concentration of Anthelmintics.
PrimaquineAminoquinolines (Antimalarial) may decrease the serum concentration of Anthelmintics.
Food InteractionsNot Available

Targets

1. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: intercalation

Components

Name UniProt ID Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Hossain M, Giri P, Suresh Kumar G: DNA Intercalation by Quinacrine and Methylene Blue: A Comparative Binding and Thermodynamic Characterization Study. DNA Cell Biol. 2007 Oct 9;. Pubmed

2. 85/88 kDa calcium-independent phospholipase A2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
85/88 kDa calcium-independent phospholipase A2 O60733 Details

References:

  1. Nuttle LC, Ligon AL, Farrell KR, Hester RL: Inhibition of phospholipase A2 attenuates functional hyperemia in the hamster cremaster muscle. Am J Physiol. 1999 Apr;276(4 Pt 2):H1289-94. Pubmed
  2. Sastry BV, Hemontolor ME, Vidaver PS, Sastry WS, Janson VE: Influence of halothane on phospholipase A2 and enzymatic methylations in the rat retinal membranes. J Ocul Pharmacol Ther. 1999 Apr;15(2):165-78. Pubmed
  3. Lohmann CH, Sagun R Jr, Sylvia VL, Cochran DL, Dean DD, Boyan BD, Schwartz Z: Surface roughness modulates the response of MG63 osteoblast-like cells to 1,25-(OH)(2)D(3) through regulation of phospholipase A(2) activity and activation of protein kinase A. J Biomed Mater Res. 1999 Nov;47(2):139-51. Pubmed
  4. Schwartz Z, Sylvia VL, Del Toro F, Hardin RR, Dean DD, Boyan BD: 24R,25-(OH)(2)D(3) mediates its membrane receptor-dependent effects on protein kinase C and alkaline phosphatase via phospholipase A(2) and cyclooxygenase-1 but not cyclooxygenase-2 in growth plate chondrocytes. J Cell Physiol. 2000 Mar;182(3):390-401. Pubmed
  5. Sylvia VL, Del Toro F, Dean DD, Hardin RR, Schwartz Z, Boyan BD: Effects of 1alpha,25-(OH)(2)D(3) on rat growth zone chondrocytes are mediated via cyclooxygenase-1 and phospholipase A(2). J Cell Biochem Suppl. 2001;Suppl 36:32-45. Pubmed

3. Cytosolic phospholipase A2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Cytosolic phospholipase A2 P47712 Details

References:

  1. Hellstrand M, Eriksson E, Nilsson CL: Dopamine D(2) receptor-induced COX-2-mediated production of prostaglandin E(2) in D(2)-transfected Chinese hamster ovary cells without simultaneous administration of a Ca(2+)-mobilizing agent. Biochem Pharmacol. 2002 Jun 15;63(12):2151-8. Pubmed
  2. Ong WY, Lu XR, Ong BK, Horrocks LA, Farooqui AA, Lim SK: Quinacrine abolishes increases in cytoplasmic phospholipase A2 mRNA levels in the rat hippocampus after kainate-induced neuronal injury. Exp Brain Res. 2003 Feb;148(4):521-4. Epub 2002 Dec 11. Pubmed
  3. Kim BC, Kim JH: Exogenous C2-ceramide activates c-fos serum response element via Rac-dependent signalling pathway. Biochem J. 1998 Mar 1;330 ( Pt 2):1009-14. Pubmed

4. Inactive phospholipase C-like protein 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Inactive phospholipase C-like protein 1 Q15111 Details

References:

  1. Biondi C, Pavan B, Ferretti ME, Corradini FG, Neri LM, Vesce F: Formyl-methionyl-leucyl-phenylalanine induces prostaglandin E2 release from human amnion-derived WISH cells by phospholipase C-mediated [Ca+]i rise. Biol Reprod. 2001 Mar;64(3):865-70. Pubmed
  2. Takuwa N, Kumada M, Yamashita K, Takuwa Y: Mechanisms of bombesin-induced arachidonate mobilization in Swiss 3T3 fibroblasts. J Biol Chem. 1991 Aug 5;266(22):14237-43. Pubmed
  3. Otamiri T: Phospholipase C-mediated intestinal mucosal damage is ameliorated by quinacrine. Food Chem Toxicol. 1989 Jun;27(6):399-402. Pubmed
  4. Noveral JP, Grunstein MM: Tachykinin regulation of airway smooth muscle cell proliferation. Am J Physiol. 1995 Sep;269(3 Pt 1):L339-43. Pubmed
  5. Bjoro T, Englund K, Torjesen PA, Haug E: Inhibitors of the arachidonic acid metabolism attenuate the thyroliberin (TRH) stimulated prolactin production without modifying the production of inositolphosphates in GH4C1 pituitary cells. Scand J Clin Lab Invest. 1993 Apr;53(2):111-6. Pubmed

Enzymes

1. Histamine N-methyltransferase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Histamine N-methyltransferase P50135 Details

References:

  1. Grassmann S, Apelt J, Sippl W, Ligneau X, Pertz HH, Zhao YH, Arrang JM, Ganellin CR, Schwartz JC, Schunack W, Stark H: Imidazole derivatives as a novel class of hybrid compounds with inhibitory histamine N-methyltransferase potencies and histamine hH3 receptor affinities. Bioorg Med Chem. 2003 May 15;11(10):2163-74. Pubmed
  2. Grassmann S, Apelt J, Sippl W, Ligneau X, Pertz HH, Zhao YH, Arrang JM, Ganellin CR, Schwartz JC, Schunack W, Stark H: Imidazole derivatives as a novel class of hybrid compounds with inhibitory histamine N-methyltransferase potencies and histamine hH3 receptor affinities. Bioorg Med Chem. 2003 May 15;11(10):2163-74. Pubmed
  3. Hui JY, Taylor SL: Inhibition of in vivo histamine metabolism in rats by foodborne and pharmacologic inhibitors of diamine oxidase, histamine N-methyltransferase, and monoamine oxidase. Toxicol Appl Pharmacol. 1985 Nov;81(2):241-9. Pubmed

2. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

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. Solute carrier family 22 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 2 O15244 Details

References:

  1. Sweet DH, Pritchard JB: rOCT2 is a basolateral potential-driven carrier, not an organic cation/proton exchanger. Am J Physiol. 1999 Dec;277(6 Pt 2):F890-8. Pubmed
  2. Dohgu S, Yamauchi A, Takata F, Sawada Y, Higuchi S, Naito M, Tsuruo T, Shirabe S, Niwa M, Katamine S, Kataoka Y: Uptake and efflux of quinacrine, a candidate for the treatment of prion diseases, at the blood-brain barrier. Cell Mol Neurobiol. 2004 Apr;24(2):205-17. Pubmed
  3. Beck WT, Cirtain MC, Glover CJ, Felsted RL, Safa AR: Effects of indole alkaloids on multidrug resistance and labeling of P-glycoprotein by a photoaffinity analog of vinblastine. Biochem Biophys Res Commun. 1988 Jun 30;153(3):959-66. Pubmed

2. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Tiberghien F, Loor F: Ranking of P-glycoprotein substrates and inhibitors by a calcein-AM fluorometry screening assay. Anticancer Drugs. 1996 Jul;7(5):568-78. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:25