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targets (2) transporters (1)
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Identification
Name Cinoxacin
Accession Number DB00827 (APRD00873)
Type small molecule
Groups approved
Description

Synthetic antimicrobial related to oxolinic acid and nalidixic acid and used in urinary tract infections. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Cinobac
Brand mixtures Not Available
Categories
  • Anti-Infective Agents
CAS number 28657-80-9
Weight Average: 262.2182
Monoisotopic: 262.05897144
Chemical Formula C12H10N2O5
InChI Key InChIKey=VDUWPHTZYNWKRN-UHFFFAOYSA-N
InChI
InChI=1S/C12H10N2O5/c1-2-14-7-4-9-8(18-5-19-9)3-6(7)11(15)10(13-14)12(16)17/h3-4H,2,5H2,1H3,(H,16,17)
Plain Text
IUPAC Name
1-ethyl-4-oxo-1H,4H,7H-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid
SMILES
CCN1N=C(C(O)=O)C(=O)C2=CC3=C(OCO3)C=C12
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Cinnolines
  • Benzodioxoles
Substructures
  • Hydroxy Compounds
  • Acetates
  • Acetals and Derivatives
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Cinnolines
  • Pyridazines
  • Carboxylic Acids and Derivatives
  • Dioxoles
  • Catechols
  • Heterocyclic compounds
  • Aromatic compounds
  • Benzodioxoles
  • Anisoles
  • Imines
  • Phenyl Esters
Pharmacology
Indication For the treatment of initial and recurrent urinary tract infections in adults caused by the following susceptible microorganisms: Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species (including K. pneumoniae), and Enterobacter species.
Pharmacodynamics Cinoxacin is a synthetic antibacterial agent with in vitro activity against many gram-negative aerobic bacteria, particularly strains of the Enterobacteriaceae family. Cinoxacin inhibits bacterial deoxyribonucleic acid (DNA) synthesis, is bactericidal, and is active over the entire urinary pH range. Cross resistance with nalidixic acid has been demonstrated.
Mechanism of action Evidence exists that cinoxacin binds strongly, but reversibly, to DNA, interfering with synthesis of RNA and, consequently, with protein synthesis. It appears to also inhibit DNA gyrase. This enzyme is necessary for proper replicated DNA separation. By inhibiting this enzyme, DNA replication and cell division is inhibited.
Absorption Rapidly absorbed after oral administration. The presence of food delays absorption but does does not affect total absorption.
Volume of distribution Not Available
Protein binding 60 to 80%
Metabolism Hepatic, with approximately 30-40% metabolized to inactive metabolites.
Route of elimination Not Available
Half life The mean serum half-life is 1.5 hours. Half-life in patients with impaired renal function may exceed 10 hours.
Clearance Not Available
Toxicity Oral, subcutaneous, and intravenous LD50 in the rat is 3610 mg/kg, 1380 mg/kg, and 860 mg/kg, respectively. Oral, subcutaneous, and intravenous LD50 in the mouse is 2330 mg/kg, 900 mg/kg, and 850 mg/kg, respectively.Symptoms following an overdose of cinoxacin may include anorexia, nausea, vomiting, epigastric distress, and diarrhea. The severity of the epigastric distress and the diarrhea are dose related. Headache, dizziness, insomnia, photophobia, tinnitus, and a tingling sensation have been reported in some patients.
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
  • Teva pharmaceuticals usa inc
Packagers Not Available
Dosage forms
Form Route Strength
Capsule Oral
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 261 dec °C PhysProp
logP 1.5 Not Available
Predicted Properties
Property Value Source
water solubility 9.61e-01 g/l ALOGPS
logP 1.25 ALOGPS
logP 1.72 ChemAxon
logS -2.4 ALOGPS
pKa (strongest acidic) 4.93 ChemAxon
pKa (strongest basic) -4.6 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 7 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 88.43 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 73.6 ChemAxon
polarizability 24.72 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00872 Link_out
KEGG Compound C08052 Link_out
PubChem Compound 2762 Link_out
PubChem Substance 46507547 Link_out
ChemSpider 2660 Link_out
ChEBI 3716 Link_out
ChEMBL 3716 Link_out
Therapeutic Targets Database DAP000999 Link_out
PharmGKB PA449007 Link_out
RxList http://www.rxlist.com/cgi/generic3/cinobac.htm Link_out
Drugs.com http://www.drugs.com/cons/cinoxacin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Cinoxacin Link_out
ATC Codes
  • J01MB06
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (37.2 KB)
MSDS show (53.7 KB)
Interactions
Drug Interactions Not Available
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. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed
  2. Drlica K, Zhao X: DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev. 1997 Sep;61(3):377-92. Pubmed
  3. Neugebauer U, Szeghalmi A, Schmitt M, Kiefer W, Popp J, Holzgrabe U: Vibrational spectroscopic characterization of fluoroquinolones. Spectrochim Acta A Mol Biomol Spectrosc. 2005 May;61(7):1505-17. Pubmed
  4. Tuma J, Connors WH, Stitelman DH, Richert C: On the effect of covalently appended quinolones on termini of DNA duplexes. J Am Chem Soc. 2002 Apr 24;124(16):4236-46. Pubmed

2. DNA

Pharmacological action: unknown
Actions: intercalation

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

Gene Sequence: FASTA

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. Tuma J, Connors WH, Stitelman DH, Richert C: On the effect of covalently appended quinolones on termini of DNA duplexes. J Am Chem Soc. 2002 Apr 24;124(16):4236-46. Pubmed
Transporters

1. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19