Identification

Name
Hexylresorcinol
Accession Number
DB11254
Type
Small Molecule
Groups
Approved
Description

Hexylresorcinol is a substituted dihydroxybenzene. It exhibits antiseptic, anthelmintic, and local anesthetic properties. It can be found in topical applications for minor skin infections and in oral solutions or throat lozenges for pain relief and first aid antiseptic.

The compound may also be used commonly in various commercial cosmetic anti-aging creams while ongoing studies research the possibility of using hexylresorcinol as an anti-cancer therapy - indications all of which require further study and testing at the current moment.

Structure
Thumb
Synonyms
  • 4-hexyl-1,3-benzenediol
  • 4-hexylresorcinol
External IDs
E-586 / INS NO.586 / INS-586 / NSC-1570
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Antiseptic Sore Throat Loz. (lemon Flavour)Lozenge2.4 mgOralH.J. Sutton Industries Ltd.1997-01-241999-03-23Canada
Antiseptic Sore Throat Loz(honey Eucalyp.fl)Lozenge2.4 mgOralH.J. Sutton Industries Ltd.1997-01-031999-03-23Canada
Antiseptic Sore Throat Loz(mint Menthol Flv)Lozenge2.4 mgOralH.J. Sutton Industries Ltd.1997-01-031999-03-23Canada
Antiseptic Throat Lozenges (with Hexylresorcinol)Lozenge2.4 mgOralH.J. Sutton Industries Ltd.1997-01-032013-07-05Canada
AvaptaSpray1 mg/1mLOralNeel Products LLC2012-08-162015-10-13Us
Bradosol Lozenges Extra Strength 3.5mgLozenge3.5 mgOralColumbia Laboratories1991-12-31Not applicableCanada
Bradosol Lozenges Extra Strength 3.5mg MintLozenge3.5 mgOralColumbia Laboratories1991-12-31Not applicableCanada
Bradosol Lozenges Regular Strength 2.4mg (cherry, Mint, Lemon, Orange, Honey-eucalyptus)Lozenge2.4 mgOralColumbia Laboratories1991-12-31Not applicableCanada
Bradosol Multiflavour Loz 2.4mgLozenge2.4 mgOralCiba Self Medication1992-12-311996-09-09Canada
Bronchodex Past.antisep.-s.miel Et Eucalypt.Lozenge2.4 mgOralProdemdis Enr.1993-12-312010-07-15Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AvaptaHexylresorcinol (1 mg/1mL) + Benzalkonium chloride (0.2 mg/1mL) + Zinc chloride (2 mg/1mL)SprayOralNeel Products LLC2012-08-162015-10-13Us
AvaptaHexylresorcinol (1 mg/1mL) + Allantoin (5 mg/1mL) + Camphor (9 mg/1mL) + Levomenthol (4 mg/1mL)SprayTopicalNeel Products LLC2012-08-062015-10-13Us
Green Guard Sore Throat ReliefHexylresorcinol (2.4 mg/1) + Levomenthol (4.5 mg/1)LozengeOralUnifirst First Aid2008-12-302015-01-26Us
Medi-First Plus Sore Throat MaxHexylresorcinol (2.4 mg/1) + Levomenthol (4.5 mg/1)LozengeOralUnifirst First Aid2008-12-302014-01-08Us
Medique SepasootheHexylresorcinol (2.4 mg/1) + Levomenthol (4.5 mg/1)LozengeOralUnifirst First Aid2011-03-082014-06-13Us
Otis Clapp ThoretsHexylresorcinol (2.4 mg/1) + Levomenthol (4.5 mg/1)LozengeOralUnifirst First Aid2008-12-302014-05-10Us
Strepsils Extra Black CherryHexylresorcinol (2.4 mg) + Levomenthol (4.0 mg)LozengeOralReckitt Benckiser2007-03-23Not applicableCanada
Categories
UNII
R9QTB5E82N
CAS number
136-77-6
Weight
Average: 194.2701
Monoisotopic: 194.13067982
Chemical Formula
C12H18O2
InChI Key
WFJIVOKAWHGMBH-UHFFFAOYSA-N
InChI
InChI=1S/C12H18O2/c1-2-3-4-5-6-10-7-8-11(13)9-12(10)14/h7-9,13-14H,2-6H2,1H3
IUPAC Name
4-hexylbenzene-1,3-diol
SMILES
CCCCCCC1=C(O)C=C(O)C=C1

Pharmacology

Indication

Hexylresorcinol is predominantly employed as the active ingredient in lotions, sprays, or lozenges indicated as a (a) topical antiseptic to help prevent skin infection in minor cuts, scrapes, or burns, or (b) as an antiseptic and local anesthetic for the relief of a sore throat and its associated pain [4, 5].

In addition, hexylresorcinol is used as an active ingredient in various commercial cosmetic skincare products as an anti-aging cream [6] while other studies have looked into whether or not the compound could be used effectively as an anti-inflammatory agent or even as an anti-cancer therapy [6].

Pharmacodynamics

Hexylresorcinol is a phenol derivative, and in typical therapeutic usage is primarily a local anesthetic for topical use on the mucous membranes of the mouth and throat [9]. The local anesthetic like properties of hexylresorcinol is likely due to its sodium channel blocking effects [9]. The agent also demonstrates mild antiseptic activity as well as an apparent anti-inflammatory, demulcent action [9].

Mechanism of action

When acting as an oral anesthetic for relieving sore throats, it is generally believed that hexylresorcinol is possibly capable of blocking voltage-gated neuronal sodium channels, which in turn would inhibit the initiation and conduction of nerve impulses for feeling or transmitting pain signals in the local area to which the hexylresorcinol is applied [10].

As an antiseptic agent, studies have demonstrated that hexylresorcinol is capable of eliciting actions like reducing or inhibiting the generation of bacterial biofilm, interfering with bacterial cell chain formation, reducing bacterial adherence of the pharynx, inhibition of glycolytic enzyme and pH drops, and alteration of cell surface hydrophobicity [2]. Unfortunately, there are either antibiotics that function even more effectively at formally treating bacterial growth or there are also other plant-derived phenolic compounds similar to hexylresorcinol that elicit stronger such mechanisms of action [2]. Nevertheless, it is useful for hexylresorcinol to have both anesthetic and certain antiseptic actions for its use in treating various relatively self-limiting scrapes and sore throats that are treated by the over-the-counter products that feature the compound. Early studies in the 1930s and 1940s suggested that there were more effective medicines over hexylresorcinol that could be employed for their anthelmintic effects [3].

As an anti-inflammatory and anti-aging agent, some studies have shown that it may be possible for hexylresorcinol to inhibit the phosphorylation of the immune response mediator NF-kappaB and also elicit a significant skin lightening effect owing to a strong inhibitory effect on tyrosinase and peroxidase and a stimulatory effect on glutathione and E-cadherin syntheses [6]. It is proposed that hexylresorcinol can bind to tyrosinase directly and inhibits its enzyme activity [6]. Literature data suggests that low glutathione levels relates to the deposition of melanin in the skin of humans and other animals, while high glutathione levels inhibit melanogenesis [6]. And ultimately, it is also reported that glutathione depletion increases tyrosinase activity in human melanoma cells, which makes hexylresorcinol's effects on tyrosinase desirable [6].

Finally, there are ongoing studies that have reported hexylresorcinol's abilities to induce the differentiation of SCC-9 squamous cell cell-line by way of the modulation of the E2F-mediated signaling pathway and suppress the growth of squamous cell carcinoma SCC-9 cells in a dose-dependent manner [6]. Moreover, such studies have also shown that hexylresorcinol is seemingly capable of dose-dependent induction of SCC-9 cell apoptosis as well as the inhibition of transglutaminase-2 enzyme activity which can facilitate chemotherapy resistance [6].

TargetActionsOrganism
UDNA topoisomerase 1
inhibitor
Human
UProtein-glutamine gamma-glutamyltransferase 2
inhibitor
Human
UTyrosinase
inhibitor
Human
Absorption

Owing to the poor absorption of hexylresorcinol, systemic exposure and symptoms are unusual [7].

Volume of distribution

Readily accessible data regarding the volume of distribution of hexylresorcinol is not available. Nevertheless, when hexylresorcinol is employed in its primary indication as a topical antiseptic or an oral anesthetic, it is generally accepted that pharmacokinetic considerations do not arise since the pharmacological action is local to the topically applied or oro-pharyngeal cavity area [5, 9, 10].

Protein binding

Readily accessible data regarding the protein binding of hexylresorcinol is not available. Nevertheless, when hexylresorcinol is employed in its primary indication as a topical antiseptic or an oral anesthetic, it is generally accepted that pharmacokinetic considerations do not arise since the pharmacological action is local to the topically applied or oro-pharyngeal cavity area [5, 9, 10].

Metabolism

Regarding the metabolism of hexylresorcinol, it has been reported that excretion of the compound in the urine is largely in the form of an ethereal sulfate conjugate [7].

Route of elimination

When two men received doses of 1 g of hexylresorcinol, an average of 18% of the dose was recovered in the urine within the first 12 hours - thereafter, the compound was not detected in urine samples [7].

Half life

Readily accessible data regarding the half-life of hexylresorcinol is not available. Nevertheless, when hexylresorcinol is employed in its primary indication as a topical antiseptic or an oral anesthetic, it is generally accepted that pharmacokinetic considerations do not arise since the pharmacological action is local to the topically applied or oro-pharyngeal cavity area [5, 9, 10].

Clearance

Readily accessible data regarding the clearance of hexylresorcinol is not available. Nevertheless, when hexylresorcinol is employed in its primary indication as a topical antiseptic or an oral anesthetic, it is generally accepted that pharmacokinetic considerations do not arise since the pharmacological action is local to the topically applied or oro-pharyngeal cavity area [5, 9, 10].

Toxicity

In the over-the-counter antiseptic and oral analgesic sprays and lozenges that hexylresorcinol is typically employed as the active ingredient, it is noted that overdosage of the agent may cause minor gastrointestinal irritation [5, 9, 10].

The probable oral LD50 of hexylresorcinol in humans has been estimated to be between 500 and 5000 mg/kg body weight, between 1 oz and 1 pint (or 1 lbs) for a 70 kg person [7, 8].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. McNally D, Shephard A, Field E: Randomised, double-blind, placebo-controlled study of a single dose of an amylmetacresol/2,4-dichlorobenzyl alcohol plus lidocaine lozenge or a hexylresorcinol lozenge for the treatment of acute sore throat due to upper respiratory tract infection. J Pharm Pharm Sci. 2012;15(2):281-94. [PubMed:22579007]
  2. Mace S, Truelstrup Hansen L, Rupasinghe HPV: Anti-Bacterial Activity of Phenolic Compounds against Streptococcus pyogenes. Medicines (Basel). 2017 May 1;4(2). pii: medicines4020025. doi: 10.3390/medicines4020025. [PubMed:28930240]
  3. Maplestone PA, Mukerji AK: Hexylresorcinol as an Anthelmintic. Ind Med Gaz. 1932 Nov;67(11):610-612. [PubMed:29011050]
  4. DailyMed: S.T.37-hexylresorcinol solution monograph [Link]
  5. Electronic Medicines Compendium: Strepsils (hexylresorcinol) Extra Triple Action Blackcurrant Lozenges Monograph [Link]
  6. Hexylresorcinol: Providing Skin Benefits by Modulating Multiple Molecular Targets [Link]
  7. NIH Toxnet: Hexylresorcinol Profile [Link]
  8. IPCS INCHEM 4-Hexylresorcinol Profile [Link]
  9. Health Products Regulatory Authority of Ireland: Summary of Product Characteristics for Hexylresorcinol [File]
  10. University of Utah College of Pharmacy: Topical Analgesic and Anaesthetic Agents Drug Class Review [File]
External Links
Human Metabolome Database
HMDB0032567
PubChem Compound
3610
PubChem Substance
347827952
ChemSpider
21106121
BindingDB
50292636
ChEBI
93749
ChEMBL
CHEMBL443605
Wikipedia
Hexylresorcinol
ATC Codes
R02AA12 — Hexylresorcinol
AHFS Codes
  • 52:04.92 — Miscellaneous Anti-infectives

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SprayOral
SprayOral1 mg/1mL
SprayTopical
SolutionTopical1.1 mg/1mL
SolutionOral; Topical1.1 mg/1mL
LozengeOral2.4 mg
LozengeOral
LozengeOral3.5 mg
LozengeOral2.4 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.454 mg/mLALOGPS
logP3.77ALOGPS
logP4.1ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)9.55ChemAxon
pKa (Strongest Basic)-5.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity58.07 m3·mol-1ChemAxon
Polarizability22.98 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-00di-0900000000-5e9f9f102fe32a7d43f9
Mass Spectrum (Electron Ionization)MSsplash10-00di-2900000000-6308ed79d3b6955a1373
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
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as resorcinols. These are compounds containing a resorcinol moiety, which is a benzene ring bearing two hydroxyl groups at positions 1 and 3.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenols
Sub Class
Benzenediols
Direct Parent
Resorcinols
Alternative Parents
1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Benzene and substituted derivatives / Organooxygen compounds / Hydrocarbon derivatives
Substituents
Resorcinol / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Monocyclic benzene moiety / Organic oxygen compound / Hydrocarbon derivative / Organooxygen compound / Aromatic homomonocyclic compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Poly(a) rna binding
Specific Function
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a singl...
Gene Name
TOP1
Uniprot ID
P11387
Uniprot Name
DNA topoisomerase 1
Molecular Weight
90725.19 Da
References
  1. Hexylresorcinol: Providing Skin Benefits by Modulating Multiple Molecular Targets [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein-glutamine gamma-glutamyltransferase activity
Specific Function
Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins.
Gene Name
TGM2
Uniprot ID
P21980
Uniprot Name
Protein-glutamine gamma-glutamyltransferase 2
Molecular Weight
77328.21 Da
References
  1. Hexylresorcinol: Providing Skin Benefits by Modulating Multiple Molecular Targets [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein homodimerization activity
Specific Function
This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the rate-limiting conversions of tyrosine to DOPA, DOPA ...
Gene Name
TYR
Uniprot ID
P14679
Uniprot Name
Tyrosinase
Molecular Weight
60392.69 Da
References
  1. Hexylresorcinol: Providing Skin Benefits by Modulating Multiple Molecular Targets [Link]

Drug created on December 03, 2015 09:51 / Updated on December 14, 2018 05:45