Banner
targets (1) transporters (1)
for drugs
Identification
Name Nalidixic Acid
Accession Number DB00779 (APRD01133)
Type small molecule
Groups approved
Description

A synthetic 1,8-naphthyridine antimicrobial agent with a limited bacteriocidal spectrum. It is an inhibitor of the A subunit of bacterial DNA gyrase. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Cybis
  • Dixiben
  • Dixinal
  • Eucistin
  • Innoxalon
  • Jicsron
  • naladixic acid
  • Nalidic acid
  • Nalidixan
  • Nalidixate
  • Nalidixic acid USP27
  • Nalidixin
  • Nalidixinic acid
  • Nalitucsan
  • Nalix
  • Nalurin
  • Naxuril
  • NegGram
  • Negram
  • Nevigramon
  • Nogram
  • Sicmylon
  • Unaserus
  • Urisal
  • Uronidix
  • Wintomylon
  • Wintron
Brand name mixtures Not Available
Categories
  • Anti-Infective Agents
  • Enzyme Inhibitors
  • Nucleic Acid Synthesis Inhibitors
CAS number 389-08-2
Weight Average: 232.2353
Monoisotopic: 232.084792260
Chemical Formula C12H12N2O3
InChI Key InChIKey=MHWLWQUZZRMNGJ-UHFFFAOYSA-N
InChI
InChI=1S/C12H12N2O3/c1-3-14-6-9(12(16)17)10(15)8-5-4-7(2)13-11(8)14/h4-6H,3H2,1-2H3,(H,16,17)
Plain Text
IUPAC Name
1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
SMILES
CCN1C=C(C(O)=O)C(=O)C2=C1N=C(C)C=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Fluoroquinolones and Quinolones
Substructures
  • Hydroxy Compounds
  • Acetates
  • Fluoroquinolones and Quinolones
  • Pyridines and Derivatives
  • Carboxylic Acids and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Imines
  • Cyanamides
Pharmacology
Indication For the treatment of urinary tract infections caused by susceptible gram-negative microorganisms, including the majority of E. Coli, Enterobacter species, Klebsiella species, and Proteus species.
Pharmacodynamics Nalidixic acid is a quinolone antibacterial agent for oral administration. Nalidixic acid has marked antibacterial activity against gram-negative bacteria including Enterobacter species, Escherichia coli, Morganella Morganii; Proteus Mirabilis, Proteus vulgaris, and Providencia rettgeri. Pseudomonas species are generally resistant to the drug. Nalidixic acid is bactericidal and is effective over the entire urinary pH range. Conventional chromosomal resistance to nalidixic acid taken in full dosage has been reported to emerge in approximately 2 to 14 percent of patients during treatment; however, bacterial resistance to nalidixic acid has not been shown to be transferable via R factor.
Mechanism of action Evidence exists for Nalidixic acid that its active metabolite, hydroxynalidixic acid, binds strongly, but reversibly, to DNA, interfering with synthesis of RNA and, consequently, with protein synthesis.
Absorption Following oral administration, nalidixic acid is rapidly absorbed from the gastrointestinal tract. Bioavailability is approximately 96%. Absorption may be delayed if taken with antacids.
Volume of distribution Not Available
Protein binding Nalidixic acid is 93% bound to protein in the blood, and the active metabolite, hydroxynalidixic acid is 63% bound.
Metabolism

Hepatic. 30% of administered dose is metabolized to the active metabolite, hydroxynalidixic acid. Rapid conjugation of parent drug and active metabolite to inactive metabolites. Metabolism may vary widely among individuals. In the urine, hydroxynalidixic acid represents 80 to 85% of the antibacterial activity.
Route of elimination Following oral administration, NegGram is rapidly absorbed from the gastrointestinal tract, partially metabolized in the liver, and rapidly excreted through the kidneys. Approximately four percent of NegGram is excreted in the feces.
Half life 1.1 to 2.5 hours in healthy adult patients, and up to 21 hours in patients with impaired renal function.
Clearance Not Available
Toxicity ORAL (LD50): Acute: 1160 mg/kg [Rat]. 572 mg/kg [Mouse]. Toxic psychosis, convulsions, increased intracranial pressure, or metabolic acidosis may occur in patients taking more than the recommended dosage. Vomiting, nausea, and lethargy may also occur following overdosage.
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
  • Mutual pharmaceutical co inc
  • Watson laboratories inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Nalidixic acid powder 7.2 USD g
Patents Not Available
Properties
State solid
Melting point 229.5 oC
Experimental Properties
Property Value Source
water solubility 100 mg/L PhysProp
logP 2.1 PhysProp
logS -3.37 [ADME Research, USCD] PhysProp
pKa 8.6 Various sources
Predicted Properties
Property Value Source
water solubility 2.30e+00 g/l ALOGPS
logP 0.95 ALOGPS
logP 1.01 ChemAxon Molconvert
logS -2.00 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 70.50 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 62.82 ChemAxon Molconvert
polarizability 23.65 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00183 Link_out
KEGG Compound C05079 Link_out
PubChem Compound 4421 Link_out
PubChem Substance 46507401 Link_out
ChemSpider 4268 Link_out
BindingDB 21691 Link_out
ChEBI 100147 Link_out
ChEMBL 100147 Link_out
Therapeutic Targets Database DAP000817 Link_out
PharmGKB PA450583 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic2/nalidixicacid.htm Link_out
Drugs.com http://www.drugs.com/cdi/nalidixic-acid.html Link_out
ATC Codes
  • J01MB02
AHFS Codes
  • 08:12.18
PDB Entries Not Available
FDA label show (47.9 KB)
MSDS show (73.2 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take with food to reduce irritation. Drink liberally.
Targets

1. DNA

Pharmacological action: yes
Actions: other

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. 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
  2. Avsaroglu MD, Helmuth R, Junker E, Hertwig S, Schroeter A, Akcelik M, Bozoglu F, Guerra B: Plasmid-mediated quinolone resistance conferred by qnrS1 in Salmonella enterica serovar Virchow isolated from Turkish food of avian origin. J Antimicrob Chemother. 2007 Sep 19;. Pubmed
  3. Jain A, Rajeswari MR: Preferential binding of quinolones to DNA with alternating G, C / A, T sequences: a spectroscopic study. J Biomol Struct Dyn. 2002 Oct;20(2):291-9. 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. Sekine T, Watanabe N, Hosoyamada M, Kanai Y, Endou H: Expression cloning and characterization of a novel multispecific organic anion transporter. J Biol Chem. 1997 Jul 25;272(30):18526-9. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:06

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.