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Record Information
Version3.6
Creation Date2012-09-06 15:16:51 UTC
Update Date2013-02-09 00:33:15 UTC
HMDB IDHMDB15235
Secondary Accession NumbersNone
Metabolite Identification
Common NameQuinacrine
DescriptionAn acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years.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
  1. Quinacrine Dihydrochloride
Chemical FormulaC23H30ClN3O
Average Molecular Weight399.957
Monoisotopic Molecular Weight399.207740304
IUPAC Name{4-[(6-chloro-2-methoxyacridin-9-yl)amino]pentyl}diethylamine
Traditional IUPAC Namequinacrine
CAS Registry Number83-89-6
SMILES
CCN(CC)CCCC(C)NC1=C2C=C(OC)C=CC2=NC2=C1C=CC(Cl)=C2
InChI Identifier
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)
InChI KeyGPKJTRJOBQGKQK-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Heteropolycyclic Compounds
ClassQuinolines and Derivatives
Sub ClassBenzoquinolines
Other Descriptors
  • Aromatic Heteropolycyclic Compounds
  • acridines(ChEBI)
Substituents
  • Alkyl Aryl Ether
  • Aminopyridine
  • Aminoquinoline
  • Anisole
  • Aryl Chloride
  • Chlorobenzene
  • Hydroxyquinoline
  • Organochloride
  • Polyamine
  • Pyridine
  • Tertiary Aliphatic Amine (Trialkylamine)
Direct ParentAcridines
Ontology
StatusExpected and Not Quantified
Origin
  • Drug
Biofunction
  • Anticestodal Agents
  • Antihelmintics
  • Antimalarials
  • Antinematodal Agents
  • Antineoplastic Agents
  • Antiprotozoals
  • Enzyme Inhibitors
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point248 - 250 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility2.39e-03 g/LNot Available
LogP5.5Not Available
Predicted Properties
PropertyValueSource
water solubility0.0024 g/LALOGPS
logP6.13ALOGPS
logP5.15ChemAxon
logS-5.2ALOGPS
pKa (strongest basic)10.33ChemAxon
physiological charge2ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count1ChemAxon
polar surface area37.39ChemAxon
rotatable bond count9ChemAxon
refractivity118.96ChemAxon
polarizability46.32ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01103
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01103
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01103
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID232
KEGG Compound IDC07339
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkQuinacrine
NuGOwiki LinkHMDB15235
Metagene LinkHMDB15235
METLIN IDNot Available
PubChem Compound237
PDB IDNot Available
ChEBI ID8711
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Bhatt RV: Camp laparoscopic sterilization deaths in Gujarat State, India, 1978-1980. Asia Oceania J Obstet Gynaecol. 1991 Dec;17(4):297-301. Pubmed: 1839351
  2. 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: 6109672
  3. 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: 6136433
  4. 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: 16623930
  5. 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: 17072963

Enzymes

General function:
Involved in metabolic process
Specific function:
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.
Gene Name:
PLA2G4A
Uniprot ID:
P47712
Molecular weight:
85210.19
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: 12110374
  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: 12582837
  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: 9480923
General function:
Involved in metabolic process
Specific function:
Catalyzes the release of fatty acids from phospholipids. It has been implicated in normal phospholipid remodeling, nitric oxide-induced or vasopressin-induced arachidonic acid release and in leukotriene and prostaglandin production. May participate in fas mediated apoptosis and in regulating transmembrane ion flux in glucose-stimulated B-cells. Has a role in cardiolipin (CL) deacylation. Required for both speed and directionality of monocyte MCP1/CCL2-induced chemotaxis through regulation of F-actin polymerization at the pseudopods. Isoform ankyrin-iPLA2-1 and isoform ankyrin-iPLA2-2, which lack the catalytic domain, are probably involved in the negative regulation of iPLA2 activity.
Gene Name:
PLA2G6
Uniprot ID:
O60733
Molecular weight:
84092.635
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: 10199854
  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: 10229494
  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: 10449625
  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: 10653606
  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: 11455568
General function:
Involved in histamine N-methyltransferase activity
Specific function:
Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine.
Gene Name:
HNMT
Uniprot ID:
P50135
Molecular weight:
6045.9
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: 12713826
  2. 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: 3933141
General function:
Involved in monooxygenase activity
Specific function:
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. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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: 19934256
General function:
Involved in monooxygenase activity
Specific function:
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.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular weight:
57108.065
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: 19934256

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
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: 8862725
General function:
Involved in ion transmembrane transporter activity
Specific function:
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
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular weight:
62564.0
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: 10600936
  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: 15176436
  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: 2898941