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Identification
Name Quinacrine
Accession Number DB01103 (APRD00317)
Type small molecule
Groups approved
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An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years.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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Quinacrine Dihydrochloride
Salts Not Available
Brand names
Name Company
Acrichine
Acrinamine
Acriquine
Akrichin
Antimalarina
Atabrine
Atebrin
Atebrine
Erion
Erion Hydrochloride
Haffkinine
Italchine
Mepacrine
Quinactine
First Prev Next Last
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Antiprotozoals
  • Antimalarials
  • Anticestodal Agents
  • Antinematodal Agents
  • Antihelmintics
CAS number 83-89-6
Weight Average: 399.957
Monoisotopic: 399.207740304
Chemical Formula C23H30ClN3O
InChI Key InChIKey=GPKJTRJOBQGKQK-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)
Plain Text
IUPAC Name
{4-[(6-chloro-2-methoxyacridin-9-yl)amino]pentyl}diethylamine
SMILES
CCN(CC)CCCC(C)NC1=C2C=C(OC)C=CC2=NC2=C1C=CC(Cl)=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Acridines
  • Hydroxyquinolines
Substructures
  • Acridines
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Pyridines and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Aminoquinolines and Derivatives
  • Halobenzenes
  • Aminopyridines and Derivatives
  • Hydroxyquinolines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • (Iso)quinolines and Derivatives
  • Phenyl Esters
Pharmacology
Indication For the treatment of giardiasis and cutaneous leishmaniasis and the management of malignant effusions.
Pharmacodynamics Quinacrine 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 action The 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.
Absorption Absorbed rapidly from the gastrointestinal tract following oral administration.
Volume of distribution Not Available
Protein binding 80-90%
Metabolism Not Available
Route of elimination Not Available
Half life 5 to 14 days
Clearance Not Available
Toxicity Oral, 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
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms Not Available
Prices
Unit description Cost Unit
Quinacrine hcl powder 8.11 USD g
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 248-250 °C Not Available
water solubility Slight Not Available
logP 5.5 Not Available
pKa 10.3 Not Available
Predicted Properties
Property Value Source
water solubility 2.39e-03 g/l ALOGPS
logP 6.13 ALOGPS
logP 5.15 ChemAxon
logS -5.2 ALOGPS
pKa (strongest basic) 10.33 ChemAxon
physiological charge 2 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 37.39 ChemAxon
rotatable bond count 9 ChemAxon
refractivity 118.96 ChemAxon
polarizability 46.32 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
KEGG Compound C07339 Link_out
PubChem Compound 237 Link_out
PubChem Substance 46507828 Link_out
ChemSpider 232 Link_out
ChEBI 8711 Link_out
ChEMBL 8711 Link_out
Therapeutic Targets Database DNC001181 Link_out
PharmGKB PA164745551 Link_out
HET QUM Link_out
Wikipedia http://en.wikipedia.org/wiki/Quinacrine Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (73.8 KB)
Interactions
Drug Interactions
Drug Interaction
Atomoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Food Interactions Not Available
Targets

1. DNA

Pharmacological action: yes
Actions: intercalation

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

Gene Sequence: FASTA

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 kDa calcium-independent phospholipase A2

Pharmacological action: yes
Actions: inhibitor

Isoform ankyrin-iPLA2-1 and isoform ankyrin-iPLA2-2, which lack the catalytic domain, are probably involved in the negative regulation of iPLA2 activity

Organism class: human
UniProt ID: O60733 Link_out
Gene: PLA2G6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory response

Organism class: human
UniProt ID: P47712 Link_out
Gene: PLA2G4A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Phospholipase C

Pharmacological action: yes
Actions: inhibitor
Organism class: human
UniProt ID: Q15111 Link_out
Gene: PLCL1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine

UniProt ID: P50135 Link_out
Gene: HNMT
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

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

3. 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. Solute carrier family 22 member 2

Actions: inhibitor

Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity

UniProt ID: O15244 Link_out
Gene: SLC22A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

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