Proflavine

Identification

Name
Proflavine
Accession Number
DB01123  (APRD00535)
Type
Small Molecule
Groups
Approved
Description

3,6-Diaminoacridine. Topical antiseptic used mainly in wound dressings. [PubChem]

Structure
Thumb
Synonyms
  • 2,8-Diaminoacridine
  • 3,6-acridinediamine
  • 3,6-diaminoacridine
  • Diaminoacridine
  • Proflavin
  • Proflavina
  • Proflavine
  • Proflavinum
Product Ingredients
IngredientUNIICASInChI Key
Proflavine hemisulfate27V8M747VB1811-28-5YADYXCVYLIKQJX-UHFFFAOYSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Kerr 100 Triple Dye Dispos-AProflavine hemisulfate (1.14 mg/mL) + Brilliant green (2.29 mg/mL) + Gentian Violet (2.2 mg/mL)SwabTopicalVista Pharm, Inc.2004-05-01Not applicableUs
Perineze Triple DyeProflavine hemisulfate (1.14 mg/.61mL) + Brilliant green (2.29 mg/.61mL) + Gentian Violet (2.29 mg/.61mL)SolutionTopicalPeace Medical Inc.2011-09-28Not applicableUs
Triple DyeProflavine hemisulfate (1.14 mg) + Brilliant green (2.29 mg) + Gentian Violet (2.29 mg)LiquidTopicalFrank W. Kerr Chemical Company1983-12-312004-10-27Canada
Categories
UNII
CY3RNB3K4T
CAS number
92-62-6
Weight
Average: 209.2465
Monoisotopic: 209.095297367
Chemical Formula
C13H11N3
InChI Key
WDVSHHCDHLJJJR-UHFFFAOYSA-N
InChI
InChI=1S/C13H11N3/c14-10-3-1-8-5-9-2-4-11(15)7-13(9)16-12(8)6-10/h1-7H,14-15H2
IUPAC Name
acridine-3,6-diamine
SMILES
NC1=CC2=NC3=C(C=CC(N)=C3)C=C2C=C1

Pharmacology

Indication

Topical antiseptic used mainly in wound dressings.

Structured Indications
Not Available
Pharmacodynamics

Proflavine is an acriflavine derivative which is a disinfectant bacteriostatic against many gram-positive bacteria. Proflavine is toxic and carcinogenic in mammals and so it is used only as a surface disinfectant or for treating superficial wounds.

Mechanism of action

Proflavine acts by interchelating DNA (intercalation), thereby disrupting DNA synthesis and leading to high levels of mutation in the copied DNA strands. This prevents bacterial reproduction.

TargetActionsOrganism
ADNA
intercalation
Human
NProthrombin
other/unknown
Human
UHTH-type transcriptional regulator QacRNot AvailableStaphylococcus aureus
UTetR family transcriptional repressor LfrRNot AvailableMycobacterium smegmatis
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB15255
KEGG Compound
C11181
PubChem Compound
7099
PubChem Substance
46505401
ChemSpider
6832
BindingDB
12590
ChEBI
8452
ChEMBL
CHEMBL55400
Therapeutic Targets Database
DAP000995
PharmGKB
PA164748742
HET
PRL
Wikipedia
Proflavine
PDB Entries
1bcu / 1qvt / 1qvu / 1vtf / 2kd4 / 2v57 / 3ft6 / 3hth / 4zph
MSDS
Download (71.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedScreeningEsophagus, Barrett1
0CompletedScreeningEsophagus, Barrett / Intraepithelial Neoplasia1
0CompletedScreeningSquamous Cell Cancer1
0RecruitingPreventionMalignant Neoplasms of Female Genital Organs1
0TerminatedScreeningAnal Intraepithelial Neoplasia (AIN) / Colon Polyps / Colonic Dysplasia1
0TerminatedScreeningEsophagus, Barrett / GERD1
2RecruitingOtherEsophagus, Barrett1
2RecruitingOtherPrior History of Squamous Cell Dysplasia and /or Neoplasia / Suspected or Known Squamous Cell Neoplasia1
2WithdrawnTreatmentUterine Cancers1
Not AvailableActive Not RecruitingPreventionCervical Cancers1
Not AvailableRecruitingDiagnosticCervical Cancers1
Not AvailableRecruitingDiagnosticCervix Carcinoma1
Not AvailableRecruitingTreatmentHead and Neck Carcinoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
SwabTopical
SolutionTopical
LiquidTopical
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)285 °CPhysProp
water solubility5E+005 mg/L (at 20 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP1.83HANSCH,C ET AL. (1995)
pKa8.06 (at 20 °C)PERRIN,DD (1972)
Predicted Properties
PropertyValueSource
Water Solubility0.104 mg/mLALOGPS
logP2.1ALOGPS
logP1.85ChemAxon
logS-3.3ALOGPS
pKa (Strongest Basic)8.32ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area64.93 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity65.46 m3·mol-1ChemAxon
Polarizability23.17 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9762
Blood Brain Barrier+0.9388
Caco-2 permeable+0.7041
P-glycoprotein substrateNon-substrate0.7289
P-glycoprotein inhibitor INon-inhibitor0.9623
P-glycoprotein inhibitor IINon-inhibitor0.8593
Renal organic cation transporterNon-inhibitor0.7993
CYP450 2C9 substrateNon-substrate0.8805
CYP450 2D6 substrateNon-substrate0.8649
CYP450 3A4 substrateNon-substrate0.7682
CYP450 1A2 substrateInhibitor0.8698
CYP450 2C9 inhibitorNon-inhibitor0.758
CYP450 2D6 inhibitorNon-inhibitor0.8692
CYP450 2C19 inhibitorNon-inhibitor0.7273
CYP450 3A4 inhibitorNon-inhibitor0.6799
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7368
Ames testAMES toxic0.9302
CarcinogenicityNon-carcinogens0.8204
BiodegradationNot ready biodegradable0.994
Rat acute toxicity2.5383 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9803
hERG inhibition (predictor II)Non-inhibitor0.7051
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.48 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as acridines. These are organic compounds containing the acridine moiety, a linear tricyclic heterocycle which consists of two benzene rings joined by a pyridine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Benzoquinolines
Direct Parent
Acridines
Alternative Parents
Aminoquinolines and derivatives / Pyridines and derivatives / Benzenoids / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Acridine / Aminoquinoline / Benzenoid / Pyridine / Heteroaromatic compound / Azacycle / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Primary amine
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aminoacridines (CHEBI:8452)

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Intercalation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 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]
  3. Sinha R, Hossain M, Kumar GS: Interaction of small molecules with double-stranded RNA: spectroscopic, viscometric, and calorimetric study of hoechst and proflavine binding to PolyCG structures. DNA Cell Biol. 2009 Apr;28(4):209-19. doi: 10.1089/dna.2008.0838. [PubMed:19364280]
  4. Berezniak EG, gladkovskaia NA, Khrebtova AS, Dukhopel'nikov EV, Zinchenko AV: [Features of binding of proflavine to DNA at different DNA-ligand concentration ratios]. Biofizika. 2009 Sep-Oct;54(5):805-12. [PubMed:19894617]
Details
2. Prothrombin
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Other/unknown
General Function
Thrombospondin receptor activity
Specific Function
Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostas...
Gene Name
F2
Uniprot ID
P00734
Uniprot Name
Prothrombin
Molecular Weight
70036.295 Da
References
  1. Sie P, Bezeaud A, Dupouy D, Archipoff G, Freyssinet JM, Dugoujon JM, Serre G, Guillin MC, Boneu B: An acquired antithrombin autoantibody directed toward the catalytic center of the enzyme. J Clin Invest. 1991 Jul;88(1):290-6. [PubMed:1711542]
  2. Koehler KA, Magnusson S: The binding of proflavin to thrombin. Arch Biochem Biophys. 1974 Jan;160(1):175-84. [PubMed:4857231]
  3. Sonder SA, Fenton JW 2nd: Proflavin binding within the fibrinopeptide groove adjacent to the catalytic site of human alpha-thrombin. Biochemistry. 1984 Apr 10;23(8):1818-23. [PubMed:6722124]
  4. Valeri AM, Wilson SM, Feinman RD: Reaction of antithrombin with proteases. Evidence for a specific reaction with papain. Biochim Biophys Acta. 1980 Aug 7;614(2):526-33. [PubMed:7407200]
  5. De Cristofaro R, De Candia E, Picozzi M, Landolfi R: Conformational transitions linked to active site ligation in human thrombin: effect on the interaction with fibrinogen and the cleavable platelet receptor. J Mol Biol. 1995 Jan 27;245(4):447-58. [PubMed:7837275]
  6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
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. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Mycobacterium smegmatis
Pharmacological action
Unknown
General Function
Dna binding
Specific Function
Not Available
Gene Name
lfrR
Uniprot ID
Q58L87
Uniprot Name
TetR family transcriptional regulator
Molecular Weight
20618.16 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 17:25