Identification
NameDequalinium
Accession NumberDB04209  (EXPT01162, DB11615)
TypeSmall Molecule
GroupsApproved
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.

Structure
Thumb
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
Product Ingredients
IngredientUNIICASInChI KeyDetails
Dequalinium acetateP8W4UX112S 4028-98-2Not applicableDetails
Dequalinium bromideNot AvailableNot AvailableNot applicableDetails
Dequalinium chlorideXYS8INN1I6 522-51-0LTNZEXKYNRNOGT-UHFFFAOYSA-NDetails
Dequalinium iodideNot AvailableNot AvailableNot applicableDetails
Dequalinium undecenoateNot AvailableNot AvailableNot applicableDetails
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DequadinLozenge0.25 mgOralBoyd Pharmaceuticals Inc.1997-04-01Not applicableCanada
Dequadin Mint Loz 0.25mgLozenge.25 mgOralGlaxo Canada Inc1985-12-311998-07-30Canada
Dequadin Oral PaintLiquid0.5 %OralBoyd Pharmaceuticals Inc.1995-12-31Not applicableCanada
Dequadin Oral Paint .5%Liquid.5 %OralGlaxo Canada Inc1958-12-311996-09-10Canada
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIIE7QC7V26B8
CAS number6707-58-0
WeightAverage: 456.6654
Monoisotopic: 456.3252973
Chemical FormulaC30H40N4
InChI KeyPCSWXVJAIHCTMO-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
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.

Structured Indications
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].

TargetKindPharmacological actionActionsOrganismUniProt ID
HTH-type transcriptional regulator QacRProteinunknownNot AvailableStaphylococcus haemolyticusP0A0N5 details
Acriflavine resistance protein BProteinunknownNot AvailableEscherichia coli (strain K12)P31224 details
E3 ubiquitin-protein ligase XIAPProteinyes
antagonist
inhibitor
HumanP98170 details
cGMP-gated cation channel alpha-1Proteinunknown
blocker
HumanP29973 details
Calcium-activated potassium channel subunit alpha-1Proteinunknown
inhibitor
HumanQ12791 details
Related Articles
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 distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
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
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
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 ]
External Links
ATC CodesR02AA02 — DequaliniumD08AH01 — DequaliniumG01AC05 — Dequalinium
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (348 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentBacterial Vaginosis (BV)1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
LozengeOral0.25 mg
LozengeOral.25 mg
LiquidOral0.5 %
LiquidOral.5 %
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
USUS4946849 A No1989-10-092002-10-01Us
Properties
StateSolid
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
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as 4-aminoquinolines. These are organic compounds containing an amino group attached to the 4-position of a quinoline ring system.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassQuinolines and derivatives
Direct Parent4-aminoquinolines
Alternative ParentsMethylpyridines / Aminopyridines and derivatives / Pyridinium derivatives / Primary aromatic amines / Benzenoids / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives / Organic cations
Substituents4-aminoquinoline / Aminopyridine / Methylpyridine / Primary aromatic amine / Pyridine / Benzenoid / Pyridinium / Heteroaromatic compound / Azacycle / Amine
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptorsquinolinium ion (CHEBI:41872 )

Targets

Kind
Protein
Organism
Staphylococcus haemolyticus
Pharmacological action
unknown
General Function:
Transcription factor activity, sequence-specific dna binding
Specific 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 (By similarity).
Gene Name:
qacR
Uniprot ID:
P0A0N5
Uniprot Name:
HTH-type transcriptional regulator QacR
Molecular Weight:
22174.175 Da
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:17139284 ]
  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:17016423 ]
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), acts downstream of BamA, the receptor for CDI. Its role in CDI is independent of the AcrA-AcrB-TolC efflux pump complex.
Gene Name:
acrB
Uniprot ID:
P31224
Uniprot Name:
Multidrug efflux pump subunit AcrB
Molecular Weight:
113572.75 Da
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:17139284 ]
  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:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonistinhibitor
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, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it ...
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
Human
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 thereby causing a depolarization of rod photoreceptors.
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
Human
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 activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key ...
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 ]
Drug created on June 13, 2005 07:24 / Updated on June 11, 2017 20:53