Resorcinol

Identification

Name
Resorcinol
Accession Number
DB11085
Type
Small Molecule
Groups
Approved
Description

Resorcinol is a 1,3-isomer (or meta-isomer) of benzenediol with the formula C6H4(OH)2. It is used as an antiseptic and disinfectant in topical pharmaceutical products in the treatment of skin disorders and infections such as acne, seborrheic dermatitis, eczema, psoriasis, corns, calluses, and warts. It exerts a keratolytic activity. Resorcinol works by helping to remove hard, scaly, or roughened skin.

Although it is primarily indicated for use as a topical application, resorcinol also possesses a well-documented anti-thyroidal activity that is generally not relied upon for any kind of formal therapeutic indication.

Structure
Thumb
Synonyms
  • 1,3-Benzenediol
  • 1,3-Dihydroxybenzene
  • 1,3-Dihydroxybenzol
  • m-Hydroquinone
  • m-hydroxyphenol
  • Resorzin
External IDs
C.I.-76505 / FEMA NO. 3589 / NSC-1571
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Acne Aid GelResorcinol (1.25 %) + Chloroxylenol (.375 %) + Octasulfur (2.5 %)GelTopicalStiefel Laboratories, Inc.1966-12-311998-07-09Canada
Acne Treatment maximum strength CVSResorcinol (2 g/100g) + Octasulfur (8 g/100g)CreamTopicalCVS Health2014-12-26Not applicableUs
Acnomel Skin Tone CreamResorcinol (2 %) + Isopropyl Alcohol (11 %) + Octasulfur (8 %)CreamTopicalNumark Laboratories, Inc.1992-12-312004-07-30Canada
Acnotex acne TreatmentResorcinol (20 mg/1mL) + Octasulfur (80 mg/1mL)LotionTopicalGenesis2011-07-072015-03-01Us
Adult AcnomelResorcinol (20 mg/1g) + Octasulfur (80 mg/1g)CreamTopicalNumark Brands, Inc1946-10-08Not applicableUs
Adult Acnomel TintedResorcinol (2 g/100g) + Octasulfur (8 g/100g)CreamTopicalDenison Inc2017-01-01Not applicableUs
Anti ItchResorcinol (2 g/100g) + Benzocaine (5 g/100g)CreamTopicalWalgreen2006-03-02Not applicableUs
Assured Feminine Anti-itchResorcinol (2 g/100g) + Benzocaine (5 g/100g)CreamTopicalGreenbrier International, Inc.2017-03-31Not applicableUs
Benzal Vagisil Creme Regular StrengthResorcinol (20 mg/1g) + Benzocaine (50 mg/1g)CreamTopicalCombe Incorporated2015-09-01Not applicableUs
BENZOCAINE and RESORCINOLResorcinol (20 mg/1g) + Benzocaine (200 mg/1g)CreamTopicalDolgencorp2009-05-19Not applicableUs
Categories
UNII
YUL4LO94HK
CAS number
108-46-3
Weight
Average: 110.1106
Monoisotopic: 110.036779436
Chemical Formula
C6H6O2
InChI Key
GHMLBKRAJCXXBS-UHFFFAOYSA-N
InChI
InChI=1S/C6H6O2/c7-5-2-1-3-6(8)4-5/h1-4,7-8H
IUPAC Name
benzene-1,3-diol
SMILES
OC1=CC(O)=CC=C1

Pharmacology

Indication

Contemporary therapeutic uses for resorcinol primarily revolve around the use of the phenol derivative as an active ingredient in topical antiseptics [2, 1, 5] or as topical antibacterial skin treatment products for conditions like acne, seborrheic dermatitis, eczema, and others [3, 2, 1, 5].

Pharmacodynamics

In vitro and in vivo studies have demonstrated that resorcinol can inhibit peroxidases in the thyroid and subsequently block the synthesis of thyroid hormones and cause goiter [5, 4]. Resorcinol interferes with the iodination of tyrosine and the oxidation of iodide [5, 4]. In an in vitro study involving lactoperoxidase (LPO) and thyroid peroxidase (TPO), it was shown that the mechanism of these two enzymes can become irreversibly inhibited by way of a suicide inactivation by resorcinol [5, 4].

It is believed that the Fe3+ of the porphyrin residue of the peroxidase to is oxidised to Fe4+ by hydrogen peroxide with the transfer of an oxygen radical [5, 4]. In LPO and TPO, the resulting π-cation radical of the porphyrin can isomerize to a radical cation with the radical in an aromatic side chain of the enzyme [5, 4]. The latter radical can bind, in a pH-dependent reaction, covalently and irreversibly to the resorcinol radical formed during regular oxidation of resorcinol and this reduces the activity of the enzyme greatly [5, 4]. While the inactivation of the enzyme and the binding of resorcinol to the enzyme may be largely increased by the presence of 0.1 nM iodide, increasing the iodide concentration to 5 mM reduced the resorcinol binding to the enzyme by one quarter but increased the enzyme activity, determined as the rate of iodination of tyrosine, more than proportionally from 6.2% to 44.7% [5, 4]. Nevertheless, the role played by iodide ions in the irreversible inactivation of the enzymes is not yet fully elucidated [5, 4].

Ultimately, such in vitro and in vivo data propose that the anti-thyroidal activity of resorcinol is caused by inhibition of thyroid peroxidase enzymes, resulting in decreased thyroid hormone production and increased proliferation due to an increase in the secretion of TSH (thyroid stimulating hormone) [5, 4]. The iodination process is catalyzed by a haem-containing enzyme, and resorcinol is known to form covalent bonds with haem [5, 4].

Despite the legitimacy of this pharmacodynamic profile in resorcinol, the therapeutic uses for which it may be formally indicated for at this time do not actually rely upon any of these mechanisms or dynamics, which are primarily elicited only upon systemic exposure to resorcinol or particularly high overdosage of the agent. This is especially true, considering resorcinol is most commonly available as topical applications to the public.

Mechanism of action

Data regarding the specific mechanisms of action of resorcinol does not appear to be readily accessible in the literature. Nevertheless, the effectiveness of the agent in treating various topical, dermatological conditions by eliciting antibacterial and keratolytic actions appears to stem from resorcinol's propensity for protein precipitation [2, 3]. In particular, it appears that resorcinol indicated for treating acne, dermatitis, or eczema in various skin care topical applications and peels revolves around the compound's ability to precipitate cutaneous proteins from the treated skin [3].

TargetActionsOrganism
UThyroid peroxidaseNot AvailableHuman
Absorption

The dermal absorption of resorcinol seems to be low (< 1%) when applied on healthy and intact skin [6]. The agent absorbed very slightly under normal conditions & the absorption was lower when applied to the scalp than to clean shaven skin due to a strong fixation by the hair [1].

Volume of distribution

Specific data regarding the volume of distribution of resorcinol is not readily available, although it is believed that the compound's volume of distribution is considered large, owing to resorcinol's profile as a lipid-soluble compound [1].

Protein binding

Specific data regarding the protein binding of resorcinol is not readily available.

Metabolism

Specific data regarding the metabolism of resorcinol is not readily available, although the major metabolite of resorcinol found in the urine was its glucuronide [1].

Route of elimination

Specific data regarding the route of elimination of resorcinol is not readily available, although the major metabolite of resorcinol found in the urine was its glucuronide [1].

Half life

Specific data regarding the half-life of resorcinol is not readily available, although, in one case of dermal exposure, an adult male with a 90% phenol exposure had an elimination half-life of about 14 hours [1].

Clearance

Specific data regarding the clearance of resorcinol is not readily available, although it is generally believed that the relatively low topical absorption or resorcinol does not result in an extensive systemic presence and clearance [6, 1].

Toxicity

Effects in man include CNS effects, mainly in persons who have used creams containing high levels of resorcinol, effects on the erythrocytes (especially methaemoglobinaemia, mainly in babies and infants) and, after prolonged exposure, effects on the thyroid gland (like goiter or especially chronic myxoedema) [5]. In addition, exogenous ochronosis is associated with prolonged exposure to resorcinol [5]. In persons suffering from resorcinol poisoning, the symptoms included anemia, spleen siderosis, and fatty degeneration of the liver and kidneys [5].

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

Interactions

Drug Interactions
DrugInteraction
AcetaminophenAcetaminophen may decrease the excretion rate of Resorcinol which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Resorcinol which could result in a higher serum level.
AlprazolamAlprazolam may decrease the excretion rate of Resorcinol which could result in a higher serum level.
AmilorideAmiloride may increase the excretion rate of Resorcinol which could result in a lower serum level and potentially a reduction in efficacy.
AmlodipineAmlodipine may decrease the excretion rate of Resorcinol which could result in a higher serum level.
AmoxicillinAmoxicillin may decrease the excretion rate of Resorcinol which could result in a higher serum level.
AmphetamineAmphetamine may decrease the excretion rate of Resorcinol which could result in a higher serum level.
AmpicillinAmpicillin may decrease the excretion rate of Resorcinol which could result in a higher serum level.
AuranofinAuranofin may decrease the excretion rate of Resorcinol which could result in a higher serum level.
BaclofenBaclofen may decrease the excretion rate of Resorcinol which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. NIH Toxnet: Resorcinol Profile [Link]
  2. Drugs.com: Resorcinol Profile [Link]
  3. Resorcinol Peel as a Part of a Facial Rejuvenation Program [Link]
  4. INCHEM: Resorcinol Profile [Link]
  5. Resorcinol - Wiley Online Library Resource [File]
  6. TUKES Finnish Safety and Chemicals Agency: Evaluation Report for Resorcinol [File]
External Links
Human Metabolome Database
HMDB0032037
KEGG Drug
D00133
KEGG Compound
C01751
PubChem Compound
5054
PubChem Substance
347827890
ChemSpider
4878
BindingDB
26189
ChEBI
27810
ChEMBL
CHEMBL24147
HET
RCO
Wikipedia
Resorcinol
ATC Codes
S01AX06 — ResorcinolD10AX02 — Resorcinol
PDB Entries
1evr / 1qiz / 2oly / 2olz / 2om0 / 2om1 / 2omh / 2omi / 2w44 / 3aqt
show 6 more
MSDS
Download (73.5 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
GelTopical
CreamTopical
PasteTopical
LiquidTopical
LotionTopical
OintmentRectal
OintmentTopical
CreamTopical125 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility82.3 mg/mLALOGPS
logP0.7ALOGPS
logP1.37ChemAxon
logS-0.13ALOGPS
pKa (Strongest Acidic)9.26ChemAxon
pKa (Strongest Basic)-5.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity30.02 m3·mol-1ChemAxon
Polarizability10.75 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
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-MSsplash10-08gi-9600000000-0e7d24e90c380c2fbaf5
GC-MS Spectrum - EI-BGC-MSsplash10-03di-9500000000-02f0a9b7ce8b4af47473
GC-MS Spectrum - EI-BGC-MSsplash10-03e9-9300000000-fcd22d3e2208eda085dd
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0f83-3960000000-6169d32b43f71f4abe1a
Mass Spectrum (Electron Ionization)MSsplash10-03di-8900000000-3771649f063971fd96f3
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
resorcinols, benzenediol (CHEBI:27810) / a benzenediol (CPD-623)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Curator comments
Interacting drug is a metabolite: oxidized metabolite of resorcinol is an irreversible inhibitor of the enzyme via covalent binding at the active site
General Function
Peroxidase activity
Specific Function
Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4).
Gene Name
TPO
Uniprot ID
P07202
Uniprot Name
Thyroid peroxidase
Molecular Weight
102961.63 Da
References
  1. Paul KB, Hedge JM, Rotroff DM, Hornung MW, Crofton KM, Simmons SO: Development of a thyroperoxidase inhibition assay for high-throughput screening. Chem Res Toxicol. 2014 Mar 17;27(3):387-99. doi: 10.1021/tx400310w. Epub 2014 Jan 14. [PubMed:24383450]

Drug created on December 03, 2015 09:51 / Updated on August 02, 2018 06:21