Dequalinium

Identification

Name
Dequalinium
Accession Number
DB04209
Description

Dequalinium is a quaternary ammonium cation that contains two quaternary quinolinium units linked by an N-decylene chain. It is an antiseptic and disinfectant agent with a broad bactericidal and fungicidal activity. It is most commonly available as a dichloride salt but is available as other various salts as well. It is used in wound dressings and mouth infections and may also have antifungal action, but may associate with skin ulceration. Dequalinium chloride is used as an active ingredient in tablets as Fluomizin for vaginal bacterial infections and in topical bacteriostat formulation as Dequadin. It has been studied for use in treatment of malaria and acute promyelocytic leukemia. Its multiple mode of action is thought to reduce the risk of resistance of pathogens.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 456.6654
Monoisotopic: 456.3252973
Chemical Formula
C30H40N4
Synonyms
  • 1,1'-(1,10-Decanediyl)bis(4-amino-2-methylquinolinium) dichloride
  • 1,1'-Decamethylenebis(4-aminoquinaldinium chloride)
  • Decamethylenebis(4-aminoquinaldinium chloride)
External IDs
  • LSM-5846

Pharmacology

Indication

Effective local treatment as vaginal tablets for infections such as fluor vaginalis, bacterial vaginosis, aerobic vaginitis, vulvo-vaginal candidiasis and trichomoniasis. Used as a topical antimicrobial agent.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Dequalinium is an antimicrobial against Gram negative and positive bacteria, yeast and protozoa. It primarily mediates this action by increasing the cell permeability with subsequent loss of enzyme activity under a rapid bactericidal and fungicidal action. The enzymatic inactivation initially might be reversible but becomes irreversible after a longer contact time between the drug and bacteria 1. The bactericidal and fungicidal effect of dequalinium chloride has been demonstrated to occur within 30–60 min 7. Dequalinium targets a broad spectrum of microorganisms including aerobic and anaerobic bacteria, as well as Candida species.

Mechanism of action

Dequalinium has a multiple mode of action. It disrupts the cell permeability of the bacteria by absorbing onto the bacterial cell surface and diffusing across the membrane. It also binds to the cytoplasmic membrane with subsequent formation of complexes and protein precipitation and lyses the membrane in adequate concentrations, perturbing osmotic exchange. Loss of normal enzymatic activity is achieved through several different processes. Denaturation of proteins results in inhibition of bacterial cell metabolism. Disruption of bacterial energy production is mediated through inhibition of glucose metabolism and inhibition of mitochondrial ATP synthesis via inhibition of bacterial F1-ATPase. Protein synthesis is also terminated at the level of ribosomes. Bacterial nucleic acids are also affected through direct binding of the drug to DNA in vitro, and precipitation of cytoplasmic material with nucleic acids being the most sensitive 1. The cationic form of dequalinium accumulates in the mitochondria and promotes anticancer activity in human leukemia cells. It mediates a cytotoxic effect by altering redox balance in cells and downregulating Raf/MEK/ERK1/2 and PI3K/Akt signaling pathways in these cells which leads to cell death by apoptosis and/or necrosis 3,4,5. Dequalinium inhibits mycothiol ligase activity in Mycobacterium tuberculosis strains 9.

TargetActionsOrganism
UAcriflavine resistance protein BNot AvailableEscherichia coli (strain K12)
AE3 ubiquitin-protein ligase XIAP
antagonist
inhibitor
Humans
UcGMP-gated cation channel alpha-1
blocker
Humans
UCalcium-activated potassium channel subunit alpha-1
inhibitor
Humans
UHTH-type transcriptional regulator QacRNot AvailableStaphylococcus aureus
Absorption

The degree of absorption is minimal in case of topical or vaginal administration thus systemic exposure is negligible. <0.1 % is absorbed systemically after oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life
Not Available
Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

The oral LD50 value of dequalinium chloride for mouse is 300mg/kg. Lethal dose (LD50) of a single intraperitoneal administration in a murine model system is 18.3 mg/kg. The majority of the adverse reactions of vaginal dequalinium tablets in clinical studies (about 90 %) were local reactions, particularly vaginal discharge, vulvovaginal pruritus, and a vaginal burning sensation. Dequalinuim is not reported to possess embryo-foetal toxicity at clinically relevant doses.

Affected organisms
  • Candida albicans and other yeasts
  • Trichomonas vaginalis, Giardia duodenalis, and Entamoeba histolytica
  • Bacteria and protozoa
  • Bacteroides
  • Peptostreptococcus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
No interactions found.

Products

Product Ingredients
IngredientUNIICASInChI Key
Dequalinium acetateP8W4UX112S4028-98-2IWYNVAJACBPVLT-UHFFFAOYSA-N
Dequalinium bromideNot AvailableNot AvailableNot applicable
Dequalinium chlorideXYS8INN1I6522-51-0LTNZEXKYNRNOGT-UHFFFAOYSA-N
Dequalinium iodideNot AvailableNot AvailableNot applicable
Dequalinium undecenoateNot AvailableNot AvailableNot applicable
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DequadinLozengeOralBoyd Pharmaceuticals Inc.1997-04-01Not applicableCanada flag
Dequadin Mint Loz 0.25mgLozengeOralGlaxo Canada Inc1985-12-311998-07-30Canada flag
Dequadin Oral PaintSolutionBuccalBoyd Pharmaceuticals Inc.1995-12-31Not applicableCanada flag
Dequadin Oral Paint .5%LiquidOralGlaxo Canada Inc1958-12-311996-09-10Canada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
D08AH01 — DequaliniumR02AA02 — DequaliniumG01AC05 — Dequalinium
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound 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
Methylpyridines / Aminopyridines and derivatives / Pyridinium derivatives / Benzenoids / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Organopnictogen compounds / Hydrocarbon derivatives / Organic cations
Substituents
4-aminoquinoline / Amine / Aminopyridine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Heteroaromatic compound / Hydrocarbon derivative / Methylpyridine / Organic cation
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
quinolinium ion (CHEBI:41872)

Chemical Identifiers

UNII
E7QC7V26B8
CAS number
6707-58-0
InChI Key
PCSWXVJAIHCTMO-UHFFFAOYSA-P
InChI
InChI=1S/C30H38N4/c1-23-21-27(31)25-15-9-11-17-29(25)33(23)19-13-7-5-3-4-6-8-14-20-34-24(2)22-28(32)26-16-10-12-18-30(26)34/h9-12,15-18,21-22,31-32H,3-8,13-14,19-20H2,1-2H3/p+2
IUPAC Name
4-amino-1-[10-(4-amino-2-methylquinolin-1-ium-1-yl)decyl]-2-methylquinolin-1-ium
SMILES
CC1=CC(N)=C2C=CC=CC2=[N+]1CCCCCCCCCC[N+]1=C(C)C=C(N)C2=C1C=CC=C2

References

General References
  1. Mendling W, Weissenbacher ER, Gerber S, Prasauskas V, Grob P: Use of locally delivered dequalinium chloride in the treatment of vaginal infections: a review. Arch Gynecol Obstet. 2016 Mar;293(3):469-84. doi: 10.1007/s00404-015-3914-8. Epub 2015 Oct 27. [PubMed:26506926]
  2. Timaner M, Bril R, Kaidar-Person O, Rachman-Tzemah C, Alishekevitz D, Kotsofruk R, Miller V, Nevelsky A, Daniel S, Raviv Z, Rotenberg SA, Shaked Y: Dequalinium blocks macrophage-induced metastasis following local radiation. Oncotarget. 2015 Sep 29;6(29):27537-54. doi: 10.18632/oncotarget.4826. [PubMed:26348470]
  3. Sancho P, Galeano E, Estan MC, Ganan-Gomez I, Boyano-Adanez Mdel C, Garcia-Perez AI: Raf/MEK/ERK signaling inhibition enhances the ability of dequalinium to induce apoptosis in the human leukemic cell line K562. Exp Biol Med (Maywood). 2012 Aug;237(8):933-42. doi: 10.1258/ebm.2012.011423. Epub 2012 Aug 8. [PubMed:22875343]
  4. Garcia-Perez AI, Galeano E, Nieto E, Sancho P: Dequalinium induces human leukemia cell death by affecting the redox balance. Leuk Res. 2011 Oct;35(10):1395-401. doi: 10.1016/j.leukres.2011.03.012. Epub 2011 Apr 8. [PubMed:21477862]
  5. Garcia-Perez AI, Galeano E, Nieto E, Estan MC, Sancho P: Dequalinium induces cytotoxicity in human leukemia NB4 cells by downregulation of Raf/MEK/ERK and PI3K/Akt signaling pathways and potentiation of specific inhibitors of these pathways. Leuk Res. 2014 Jul;38(7):795-803. doi: 10.1016/j.leukres.2014.01.009. Epub 2014 Jan 28. [PubMed:24811390]
  6. Della Casa V, Noll H, Gonser S, Grob P, Graf F, Pohlig G: Antimicrobial activity of dequalinium chloride against leading germs of vaginal infections. Arzneimittelforschung. 2002;52(9):699-705. [PubMed:12404886]
  7. D'Auria FD, Simonetti G, Strippoli V: [Antimicrobial characteristics of a tincture of dequalinium chloride]. Ann Ig. 1989 Sep-Oct;1(5):1227-41. [PubMed:2483904]
  8. Weiss MJ, Wong JR, Ha CS, Bleday R, Salem RR, Steele GD Jr, Chen LB: Dequalinium, a topical antimicrobial agent, displays anticarcinoma activity based on selective mitochondrial accumulation. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5444-8. [PubMed:3474661]
  9. Gutierrez-Lugo MT, Baker H, Shiloach J, Boshoff H, Bewley CA: Dequalinium, a new inhibitor of Mycobacterium tuberculosis mycothiol ligase identified by high-throughput screening. J Biomol Screen. 2009 Jul;14(6):643-52. doi: 10.1177/1087057109335743. Epub 2009 Jun 12. [PubMed:19525487]
  10. Gamboa-Vujicic G, Emma DA, Liao SY, Fuchtner C, Manetta A: Toxicity of the mitochondrial poison dequalinium chloride in a murine model system. J Pharm Sci. 1993 Mar;82(3):231-5. [PubMed:8450414]
PubChem Compound
2993
PubChem Substance
46507206
ChemSpider
2886
BindingDB
50048403
RxNav
3226
ChEBI
41872
ChEMBL
CHEMBL333826
ZINC
ZINC000001655706
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
DEQ
Drugs.com
Drugs.com Drug Page
Wikipedia
Dequalinium
AHFS Codes
  • 52:04.92 — Miscellaneous Anti-infectives
PDB Entries
1jt6 / 1oyd / 3arp / 3art / 3br1 / 3br2 / 3bt9 / 3btj / 3vw0
MSDS
Download (348 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentVulvovaginal Candidiasis1
3CompletedTreatmentBacterial Vaginosis (BV)1
Not AvailableCompletedNot AvailableBacterial Vaginoses1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral15 mg
Lozenge250 mcg
SolutionBuccal
LiquidOral
Lozenge50 mg
SuppositoryVaginal10 mg
TabletVaginal
TabletVaginal10 mg
PastilleOral0.25 MG
LozengeOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US4946849No1990-08-072002-10-01US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)Decomposes at 326ºCMSDS
Predicted Properties
PropertyValueSource
Water Solubility4.77e-07 mg/mLALOGPS
logP0.16ALOGPS
logP-3.6ChemAxon
logS-9ALOGPS
pKa (Strongest Basic)-0.34ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area59.8 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity147 m3·mol-1ChemAxon
Polarizability56.76 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.5208
Blood Brain Barrier+0.924
Caco-2 permeable+0.5756
P-glycoprotein substrateSubstrate0.6725
P-glycoprotein inhibitor INon-inhibitor0.7203
P-glycoprotein inhibitor IIInhibitor0.7281
Renal organic cation transporterInhibitor0.6769
CYP450 2C9 substrateNon-substrate0.8745
CYP450 2D6 substrateNon-substrate0.5072
CYP450 3A4 substrateNon-substrate0.5434
CYP450 1A2 substrateNon-inhibitor0.6703
CYP450 2C9 inhibitorNon-inhibitor0.9119
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorInhibitor0.6677
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5512
Ames testAMES toxic0.5875
CarcinogenicityNon-carcinogens0.9063
BiodegradationNot ready biodegradable0.9969
Rat acute toxicity2.6736 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.823
hERG inhibition (predictor II)Inhibitor0.9123
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
General Function
Identical protein binding
Specific Function
AcrA-AcrB-AcrZ-TolC is a drug efflux protein complex with broad substrate specificity that uses the proton motive force to export substrates.Involved in contact-dependent growth inhibition (CDI), a...
Gene Name
acrB
Uniprot ID
P31224
Uniprot Name
Multidrug efflux pump subunit AcrB
Molecular Weight
113572.75 Da
References
  1. Yu EW, Aires JR, McDermott G, Nikaido H: A periplasmic drug-binding site of the AcrB multidrug efflux pump: a crystallographic and site-directed mutagenesis study. J Bacteriol. 2005 Oct;187(19):6804-15. doi: 10.1128/JB.187.19.6804-6815.2005. [PubMed:16166543]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Zinc ion binding
Specific Function
Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation,...
Gene Name
XIAP
Uniprot ID
P98170
Uniprot Name
E3 ubiquitin-protein ligase XIAP
Molecular Weight
56684.41 Da
References
  1. Orzaez M, Gortat A, Sancho M, Carbajo RJ, Pineda-Lucena A, Palacios-Rodriguez Y, Perez-Paya E: Characterization of dequalinium as a XIAP antagonist that targets the BIR2 domain. Apoptosis. 2011 May;16(5):460-7. doi: 10.1007/s10495-011-0582-4. [PubMed:21340509]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Blocker
General Function
Voltage-gated potassium channel activity
Specific Function
Visual signal transduction is mediated by a G-protein coupled cascade using cGMP as second messenger. This protein can be activated by cyclic GMP which leads to an opening of the cation channel and...
Gene Name
CNGA1
Uniprot ID
P29973
Uniprot Name
cGMP-gated cation channel alpha-1
Molecular Weight
79584.825 Da
References
  1. Rosenbaum T, Islas LD, Carlson AE, Gordon SE: Dequalinium: a novel, high-affinity blocker of CNGA1 channels. J Gen Physiol. 2003 Jan;121(1):37-47. [PubMed:12508052]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity
Specific Function
Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activati...
Gene Name
KCNMA1
Uniprot ID
Q12791
Uniprot Name
Calcium-activated potassium channel subunit alpha-1
Molecular Weight
137558.115 Da
References
  1. Castle NA, Haylett DG, Morgan JM, Jenkinson DH: Dequalinium: a potent inhibitor of apamin-sensitive K+ channels in hepatocytes and of nicotinic responses in skeletal muscle. Eur J Pharmacol. 1993 May 19;236(2):201-7. [PubMed:8100530]
Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
Unknown
General Function
Transcriptional repressor of qacA. Binds to IR1, an unusually long 28 bp operator, which is located downstream from the qacA promoter and overlaps its transcription start site. QacR is induced from its IR1 site by binding to one of many structurally dissimilar cationic lipophilic compounds, which are also substrates of QacA.
Specific Function
Dna binding
Gene Name
qacR
Uniprot ID
P0A0N4
Uniprot Name
HTH-type transcriptional regulator QacR
Molecular Weight
22174.175 Da
References
  1. Peters KM, Schuman JT, Skurray RA, Brown MH, Brennan RG, Schumacher MA: QacR-cation recognition is mediated by a redundancy of residues capable of charge neutralization. Biochemistry. 2008 Aug 5;47(31):8122-9. doi: 10.1021/bi8008246. Epub 2008 Jul 11. [PubMed:18616285]
  2. Murray DS, Schumacher MA, Brennan RG: Crystal structures of QacR-diamidine complexes reveal additional multidrug-binding modes and a novel mechanism of drug charge neutralization. J Biol Chem. 2004 Apr 2;279(14):14365-71. doi: 10.1074/jbc.M313870200. Epub 2004 Jan 15. [PubMed:14726520]

Drug created on June 13, 2005 07:24 / Updated on October 21, 2020 01:55

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