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Identification
Name Enoxacin
Accession Number DB00467 (APRD00947)
Type small molecule
Groups approved
Description

A broad-spectrum 6-fluoronaphthyridinone antibacterial agent (fluoroquinolones) structurally related to nalidixic acid. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Penetrex
Brand mixtures Not Available
Categories
  • Anti-Infective Agents
  • Nucleic Acid Synthesis Inhibitors
CAS number 74011-58-8
Weight Average: 320.3189
Monoisotopic: 320.128468635
Chemical Formula C15H17FN4O3
InChI Key InChIKey=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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Fluoroquinolones and Quinolones
Substructures
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Pyridines and Derivatives
  • Piperazines
  • Carboxylic Acids and Derivatives
  • Aminopyridines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Cyanamides
  • Aryl Halides
  • Fluoroquinolones and Quinolones
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).
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
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
Packagers Not Available
Dosage forms
Form Route Strength
Tablet, film coated Oral
Prices Not Available
Patents Not Available
Properties
State solid
Melting point 220-224 oC
Experimental Properties
Property Value Source
water solubility 3.43 g/L PhysProp
logP 2.3 PhysProp
Predicted Properties
Property Value Source
water solubility 1.09e+00 g/l ALOGPS
logP -0.97 ALOGPS
logP -0.98 ChemAxon Molconvert
logS -2.5 ALOGPS
pKa 0 ChemAxon Molconvert
hydrogen acceptor count 7 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 85.77 ChemAxon Molconvert
rotatable bond count 3 ChemAxon Molconvert
refractivity 83.95 ChemAxon Molconvert
polarizability 31.63 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00310 Link_out
KEGG Compound C06979 Link_out
PubChem Compound 3229 Link_out
PubChem Substance 46507505 Link_out
ChemSpider 3116 Link_out
ChEBI 157175 Link_out
ChEMBL 157175 Link_out
Therapeutic Targets Database DAP001000 Link_out
PharmGKB PA449462 Link_out
RxList http://www.rxlist.com/cgi/generic2/enoxacin.htm Link_out
Drugs.com http://www.drugs.com/mtm/enoxacin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Enoxacin Link_out
ATC Codes
  • J01MA04
  • J01MA19
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (44.5 KB)
Interactions
Drug Interactions
Drug Interaction
Aminophylline Enoxacin may increase the effect of aminophylline.
Calcium Formation of non-absorbable complexes
Cimetidine Cimetidine may decrease the absorption of enoxacin.
Esomeprazole Esomeprazole may decrease the absorption of enoxacin.
Famotidine Famotidine may decrease the absorption of enoxacin.
Iron Dextran Formation of non-absorbable complexes
Lansoprazole Lansoprazole may decrease the absorption of enoxacin.
Magnesium Formation of non-absorbable complexes
Nizatidine Nizatidine may decrease the absorption of enoxacin.
Omeprazole Omeprazole may decrease the absorption of enoxacin.
Oxtriphylline Enoxacin may increase the effect of oxtriphylline.
Pantoprazole Pantoprazole may decrease the absorption of enoxacin.
Rabeprazole Rabeprazole may decrease the absorption of enoxacin.
Ramelteon Enoxacin increases levels/toxicity of ramelteon
Theophylline Enoxacin may increase the effect of theophylline.
Food Interactions Not Available
Targets

1. DNA gyrase subunit A

Pharmacological action: yes
Actions: inhibitor

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

Organism class: bacterial
UniProt ID: P43700 Link_out
Gene: gyrA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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
  6. Neuman M: Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988 Feb;14(2):96-121. Pubmed
  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

2. DNA topoisomerase 4 subunit A

Pharmacological action: yes
Actions: inhibitor

Topoisomerase IV is essential for chromosome segregation. It has relaxation of supercoiled DNA activity. Performs the decatenation events required during the replication of a circular DNA molecule

Organism class: bacterial
UniProt ID: P43702 Link_out
Gene: parC
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Neuman M: Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988 Feb;14(2):96-121. Pubmed
  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

3. DNA topoisomerase 2-alpha

Pharmacological action: no
Actions: inhibitor

Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks

Organism class: human
UniProt ID: P11388 Link_out
Gene: TOP2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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. Pubmed
  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
Enzymes

1. Cytochrome P450 1A2

Actions: inhibitor

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 N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 14, 2012 11:42