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Identification
NamePefloxacin
Accession NumberDB00487  (APRD00108)
TypeSmall Molecule
GroupsApproved
Description

A synthetic broad-spectrum fluoroquinolone antibacterial agent active against most gram-negative and gram-positive bacteria. [PubChem]

Structure
Thumb
Synonyms
Labocton
Pefloxacin
Pefloxacine
Pefloxacino
Pefloxacinum
PFLX
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
LaboctonNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Pefloxacin mesylate dihydrate
ThumbNot applicableDBSALT000852
Categories
UNII2H52Z9F2Q5
CAS number70458-92-3
WeightAverage: 333.3574
Monoisotopic: 333.148869726
Chemical FormulaC17H20FN3O3
InChI KeyInChIKey=FHFYDNQZQSQIAI-UHFFFAOYSA-N
InChI
InChI=1S/C17H20FN3O3/c1-3-20-10-12(17(23)24)16(22)11-8-13(18)15(9-14(11)20)21-6-4-19(2)5-7-21/h8-10H,3-7H2,1-2H3,(H,23,24)
IUPAC Name
1-ethyl-6-fluoro-7-(4-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
SMILES
CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(C=C12)N1CCN(C)CC1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as quinoline carboxylic acids. These are quinolines in which the quinoline ring system is substituted by a carboxyl group at one or more positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassQuinoline carboxylic acids
Direct ParentQuinoline carboxylic acids
Alternative Parents
Substituents
  • Quinoline-3-carboxylic acid
  • N-arylpiperazine
  • Fluoroquinolone
  • Dihydroquinolone
  • Aminoquinoline
  • Dihydroquinoline
  • Pyridine carboxylic acid or derivatives
  • Pyridine carboxylic acid
  • Dialkylarylamine
  • N-alkylpiperazine
  • N-methylpiperazine
  • Benzenoid
  • Pyridine
  • Piperazine
  • 1,4-diazinane
  • Aryl halide
  • Aryl fluoride
  • Heteroaromatic compound
  • Vinylogous amide
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of uncomplicated gonococcal urethritis in males and for gram-negative-bacterial infections in the gastrointestinal system and the genitourinary tract.
PharmacodynamicsPefloxacin is a fluoroquinolone antibiotic. Flouroquinolones such as pefloxacin possess excellent activity against gram-negative aerobic bacteria such as E.coli and Neisseria gonorrhoea as well as gram-positive bacteria including S. pneumoniae and Staphylococcus aureus. They also posses effective activity against shigella, salmonella, campylobacter, gonococcal organisms, and multi drug resistant pseudomonas and enterobacter.
Mechanism of actionThe bactericidal action of pefloxacin results from interference with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. DNA gyrase appears to be the primary quinolone target for gram-negative bacteria. Topoisomerase IV appears to be the preferential target in gram-positive organisms. Interference with these two topoisomerases results in strand breakage of the bacterial chromosome, supercoiling, and resealing. As a result DNA replication and transcription is inhibited.
Related Articles
AbsorptionWell absorbed by the oral route.
Volume of distributionNot Available
Protein binding20-30%
Metabolism

Hepatic. Primary metabolites are pefloxacin N-oxide and norfloxacin.

SubstrateEnzymesProduct
Pefloxacin
Not Available
NorfloxacinDetails
Pefloxacin
Not Available
Pefloxacin N-oxideDetails
Route of eliminationNot Available
Half life8.6 hours
ClearanceNot Available
ToxicityAdverse reactions include peripheral neuropathy, nervousness, agitation, anxiety, and phototoxic events (rash, itching, burning) due to sunlight exposure.
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9914
Blood Brain Barrier-0.9651
Caco-2 permeable+0.9002
P-glycoprotein substrateSubstrate0.8136
P-glycoprotein inhibitor INon-inhibitor0.8781
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.6812
CYP450 2C9 substrateNon-substrate0.8645
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6809
CYP450 1A2 substrateNon-inhibitor0.9275
CYP450 2C9 inhibitorNon-inhibitor0.9206
CYP450 2D6 inhibitorNon-inhibitor0.9112
CYP450 2C19 inhibitorNon-inhibitor0.8584
CYP450 3A4 inhibitorNon-inhibitor0.9524
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6784
Ames testAMES toxic0.9108
CarcinogenicityNon-carcinogens0.8816
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.9255 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7983
hERG inhibition (predictor II)Non-inhibitor0.7795
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point271 dec °CPhysProp
water solubility11.4 mg/mL at 25 °CNot Available
logP0.27HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility1.23 mg/mLALOGPS
logP0.2ALOGPS
logP0.88ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)5.66ChemAxon
pKa (Strongest Basic)6.47ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area64.09 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity90.77 m3·mol-1ChemAxon
Polarizability34.42 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

DrugSyn.org

US4292317
General ReferencesNot Available
External Links
ATC CodesJ01MA03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
yes
Actions
inhibitor
General Function:
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function:
Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.
Gene Name:
parC
Uniprot ID:
P43702
Molecular Weight:
83366.24 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. Varon E, Houssaye S, Grondin S, Gutmann L: Nonmolecular test for detection of low-level resistance to fluoroquinolones in Streptococcus pneumoniae. Antimicrob Agents Chemother. 2006 Feb;50(2):572-9. [PubMed:16436712 ]
  4. Rafii F, Park M, Novak JS: Alterations in DNA gyrase and topoisomerase IV in resistant mutants of Clostridium perfringens found after in vitro treatment with fluoroquinolones. Antimicrob Agents Chemother. 2005 Feb;49(2):488-92. [PubMed:15673722 ]
  5. Vila J, Sanchez-Cespedes J, Sierra JM, Piqueras M, Nicolas E, Freixas J, Giralt E: Antibacterial evaluation of a collection of norfloxacin and ciprofloxacin derivatives against multiresistant bacteria. Int J Antimicrob Agents. 2006 Jul;28(1):19-24. Epub 2006 Jun 14. [PubMed:16781123 ]
  6. Oyamada Y, Ito H, Fujimoto K, Asada R, Niga T, Okamoto R, Inoue M, Yamagishi J: Combination of known and unknown mechanisms confers high-level resistance to fluoroquinolones in Enterococcus faecium. J Med Microbiol. 2006 Jun;55(Pt 6):729-36. [PubMed:16687591 ]
Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
yes
Actions
inhibitor
General Function:
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function:
DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.
Gene Name:
gyrA
Uniprot ID:
P43700
Molecular Weight:
97817.145 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. Gootz TD, Zaniewski RP, Haskell SL, Kaczmarek FS, Maurice AE: Activities of trovafloxacin compared with those of other fluoroquinolones against purified topoisomerases and gyrA and grlA mutants of Staphylococcus aureus. Antimicrob Agents Chemother. 1999 Aug;43(8):1845-55. [PubMed:10428901 ]
  4. Bebear CM, Renaudin H, Charron A, Bove JM, Bebear C, Renaudin J: Alterations in topoisomerase IV and DNA gyrase in quinolone-resistant mutants of Mycoplasma hominis obtained in vitro. Antimicrob Agents Chemother. 1998 Sep;42(9):2304-11. [PubMed:9736554 ]
  5. Varon E, Houssaye S, Grondin S, Gutmann L: Nonmolecular test for detection of low-level resistance to fluoroquinolones in Streptococcus pneumoniae. Antimicrob Agents Chemother. 2006 Feb;50(2):572-9. [PubMed:16436712 ]
  6. Hombrouck C, Capmau ML, Moreau N: Overexpression, purification and photoaffinity labeling with a 3H-analogue of norfloxacin, of the GyrA and GyrB subunits of the DNA gyrase. Cell Mol Biol (Noisy-le-grand). 1999 May;45(3):347-52. [PubMed:10386791 ]
  7. Hooper DC: Quinolone mode of action--new aspects. Drugs. 1993;45 Suppl 3:8-14. [PubMed:7689456 ]
  8. Fukuda H, Hori S, Hiramatsu K: Antibacterial activity of gatifloxacin (AM-1155, CG5501, BMS-206584), a newly developed fluoroquinolone, against sequentially acquired quinolone-resistant mutants and the norA transformant of Staphylococcus aureus. Antimicrob Agents Chemother. 1998 Aug;42(8):1917-22. [PubMed:9687384 ]
  9. Drlica K, Zhao X: DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev. 1997 Sep;61(3):377-92. [PubMed:9293187 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Ubiquitin binding
Specific Function:
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Gene Name:
TOP2A
Uniprot ID:
P11388
Molecular Weight:
174383.88 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
unknown
General Function:
Magnesium ion binding
Specific Function:
Releases the supercoiling and torsional tension of DNA, which is introduced during the DNA replication and transcription, by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(...
Gene Name:
topA
Uniprot ID:
Q06AK7
Molecular Weight:
79099.16 Da
References
  1. Tabary X, Moreau N, Dureuil C, Le Goffic F: Effect of DNA gyrase inhibitors pefloxacin, five other quinolones, novobiocin, and clorobiocin on Escherichia coli topoisomerase I. Antimicrob Agents Chemother. 1987 Dec;31(12):1925-8. [PubMed:2830840 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23