Identification

Name
Enoxacin
Accession Number
DB00467  (APRD00947)
Type
Small Molecule
Groups
Approved, Investigational
Description

A broad-spectrum 6-fluoronaphthyridinone antibacterial agent (fluoroquinolones) structurally related to nalidixic acid. [PubChem]

Structure
Thumb
Synonyms
  • 1-Ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3-carboxylic acid
  • 1-Ethyl-6-fluoro-4-oxo-7-piperazin-1-yl-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid
  • Enoxacin
  • Enoxacina
  • Énoxacine
  • Enoxacino
  • Enoxacinum
External IDs
AT 2266 / AT-2266 / CI 919 / CI-919 / PD 107779 / PD-107779
International/Other Brands
Almitil / Bactidan / Comprecin / Enoksetin / Enoxen / Enoxin / Enoxor (Pierre Fabre) / Enroxil / Flumark / Gyramid / Penetrex / Vinone
Categories
UNII
325OGW249P
CAS number
74011-58-8
Weight
Average: 320.3189
Monoisotopic: 320.128468635
Chemical Formula
C15H17FN4O3
InChI Key
IDYZIJYBMGIQMJ-UHFFFAOYSA-N
InChI
InChI=1S/C15H17FN4O3/c1-2-19-8-10(15(22)23)12(21)9-7-11(16)14(18-13(9)19)20-5-3-17-4-6-20/h7-8,17H,2-6H2,1H3,(H,22,23)
IUPAC Name
1-ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
SMILES
CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(N=C12)N1CCNCC1

Pharmacology

Indication

For the treatment of adults (≥18 years of age) with the following infections caused by susceptible strains of the designated microorganisms: (1) uncomplicated urethral or cervical gonorrhea due to Neisseria gonorrhoeae, (2) uncomplicated urinary tract infections (cystitis) due to Escherichia coli, Staphylococcus epidermidis, or Staphylococcus saprophyticus, and (3) complicated urinary tract infections due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus epidermidis, or Enterobacter cloacae.

Pharmacodynamics

Enoxacin is a quinolone/fluoroquinolone antibiotic. Enoxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Enoxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. Enoxacin may be active against pathogens resistant to drugs that act by different mechanisms.

Mechanism of action

Enoxacin exerts its bactericidal action via the inhibition of the essential bacterial enzyme DNA gyrase (DNA Topoisomerase II).

TargetActionsOrganism
ADNA gyrase subunit A
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
ADNA topoisomerase 4 subunit A
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
NDNA topoisomerase 2-alpha
inhibitor
Human
Absorption

Rapidly absorbed following oral administration, with an absolute oral bioavailability of approximately 90%.

Volume of distribution
Not Available
Protein binding

Enoxacin is approximately 40% bound to plasma proteins in healthy subjects and is approximately 14% bound to plasma proteins in patients with impaired renal function.

Metabolism

Hepatic. Some isozymes of the cytochrome P-450 hepatic microsomal enzyme system are inhibited by enoxacin. After a single dose, greater than 40% was recovered in urine by 48 hours as unchanged drug.

Route of elimination
Not Available
Half life

Plasma half-life is 3 to 6 hours.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limonene(4R)-limonene may increase the neuroexcitatory activities of Enoxacin.
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when 16-Bromoepiandrosterone is combined with Enoxacin.
19-norandrostenedioneThe risk or severity of adverse effects can be increased when 19-norandrostenedione is combined with Enoxacin.
5-androstenedioneThe risk or severity of adverse effects can be increased when 5-androstenedione is combined with Enoxacin.
AcarboseThe therapeutic efficacy of Acarbose can be increased when used in combination with Enoxacin.
AceclofenacAceclofenac may increase the neuroexcitatory activities of Enoxacin.
AcemetacinAcemetacin may increase the neuroexcitatory activities of Enoxacin.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be increased when used in combination with Enoxacin.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Enoxacin.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Enoxacin.
Food Interactions
Not Available

References

Synthesis Reference
US4359578
General References
Not Available
External Links
Human Metabolome Database
HMDB0014610
KEGG Drug
D00310
KEGG Compound
C06979
PubChem Compound
3229
PubChem Substance
46507505
ChemSpider
3116
BindingDB
50296358
ChEBI
157175
ChEMBL
CHEMBL826
Therapeutic Targets Database
DAP001000
PharmGKB
PA449462
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Enoxacin
ATC Codes
J01MA04 — Enoxacin
MSDS
Download (44.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1

Pharmacoeconomics

Manufacturers
  • Sanofi aventis us llc
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)220-224 °CPhysProp
water solubility3.43 g/LNot Available
logP-0.20SANGSTER (1994) (ION-CORRECT)
Predicted Properties
PropertyValueSource
Water Solubility1.09 mg/mLALOGPS
logP-0.97ALOGPS
logP-0.98ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)5.5ChemAxon
pKa (Strongest Basic)8.59ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area85.77 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity83.95 m3·mol-1ChemAxon
Polarizability31.63 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.995
Blood Brain Barrier-0.9659
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.8683
P-glycoprotein inhibitor INon-inhibitor0.8978
P-glycoprotein inhibitor IINon-inhibitor0.8606
Renal organic cation transporterNon-inhibitor0.7736
CYP450 2C9 substrateNon-substrate0.8078
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateNon-substrate0.7557
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8862
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5351
Ames testAMES toxic0.9124
CarcinogenicityNon-carcinogens0.802
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.8383 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6527
hERG inhibition (predictor II)Non-inhibitor0.5448
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-0009000000-c343d2455564f9c283ab
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-0039000000-c8fb064ca8dcd22fd051
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-0069000000-6f1cc68c72c995af1700
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-05fr-0195000000-f089fb10889524908bb9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0391000000-342a8fc923e2f74b2c2f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0970000000-ad4c54479d1e64d34d71
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0pc0-2691000000-70495182f5d53b3e2f3e

Taxonomy

Description
This compound belongs to the class of organic compounds known as naphthyridine carboxylic acids and derivatives. These are compounds containing a naphthyridine moiety, where one of the ring atoms bears a carboxylic acid group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Naphthyridines
Direct Parent
Naphthyridine carboxylic acids and derivatives
Alternative Parents
Pyridinylpiperazines / N-arylpiperazines / Fluoroquinolones / Pyridinecarboxylic acids / Dialkylarylamines / Aminopyridines and derivatives / Aryl fluorides / Imidolactams / Vinylogous amides / Heteroaromatic compounds
show 10 more
Substituents
Naphthyridine carboxylic acid / Fluoroquinolone / N-arylpiperazine / Pyridinylpiperazine / Pyridine carboxylic acid / Pyridine carboxylic acid or derivatives / Dialkylarylamine / Aminopyridine / Aryl fluoride / Aryl halide
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
N-arylpiperazine, monocarboxylic acid, amino acid, 1,8-naphthyridine derivative, quinolone antibiotic, fluoroquinolone antibiotic (CHEBI:157175)

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
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, inc...
Gene Name
gyrA
Uniprot ID
P43700
Uniprot Name
DNA gyrase subunit A
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. Yoshida H, Nakamura M, Bogaki M, Ito H, Kojima T, Hattori H, Nakamura S: Mechanism of action of quinolones against Escherichia coli DNA gyrase. Antimicrob Agents Chemother. 1993 Apr;37(4):839-45. [PubMed:8388200]
  4. Weisser J, Wiedemann B: Elimination of plasmids by enoxacin and ofloxacin at near inhibitory concentrations. J Antimicrob Chemother. 1986 Nov;18(5):575-83. [PubMed:3542924]
  5. Courtright JB, Turowski DA, Sonstein SA: Alteration of bacterial DNA structure, gene expression, and plasmid encoded antibiotic resistance following exposure to enoxacin. J Antimicrob Chemother. 1988 Feb;21 Suppl B:1-18. [PubMed:2834313]
  6. Neuman M: Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988 Feb;14(2):96-121. [PubMed:3282749]
  7. Castora FJ, Vissering FF, Simpson MV: The effect of bacterial DNA gyrase inhibitors on DNA synthesis in mammalian mitochondria. Biochim Biophys Acta. 1983 Sep 9;740(4):417-27. [PubMed:6309236]
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
Uniprot Name
DNA topoisomerase 4 subunit A
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. Neuman M: Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988 Feb;14(2):96-121. [PubMed:3282749]
  4. Takahashi H, Hayakawa I, Akimoto T: [The history of the development and changes of quinolone antibacterial agents]. Yakushigaku Zasshi. 2003;38(2):161-79. [PubMed:15143768]
Kind
Protein
Organism
Human
Pharmacological action
No
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 segr...
Gene Name
TOP2A
Uniprot ID
P11388
Uniprot Name
DNA topoisomerase 2-alpha
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]
  2. Maki T, Hirono I, Kondo H, Aoki T: Drug resistance mechanism of the fish-pathogenic bacterium Lactococcus garvieae. J Fish Dis. 2008 Jun;31(6):461-8. doi: 10.1111/j.1365-2761.2008.00927.x. [PubMed:18471102]
  3. Snyder RD, Cooper CS: Photogenotoxicity of fluoroquinolones in Chinese hamster V79 cells: dependency on active topoisomerase II. Photochem Photobiol. 1999 Mar;69(3):288-93. [PubMed:10089819]

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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
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]
  2. Drug Interactions & Labeling - FDA [Link]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 12:48