Nalidixic acid

Nalidixic acid
Clinical data
Trade namesNegGram, Wintomylon, others
AHFS/Drugs.comConsumer Drug Information
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • US: Not FDA approved
Pharmacokinetic data
Protein binding90%
MetabolismPartially Hepatic
Elimination half-life6-7 hours, significantly longer in renal impairment
Identifiers
  • 1-Ethyl-7-methyl-4-oxo-[1,8]naphthyridine-3-carboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.006.241 Edit this at Wikidata
Chemical and physical data
FormulaC12H12N2O3
Molar mass232.239 g·mol−1
3D model (JSmol)
  • O=C\2c1c(nc(cc1)C)N(/C=C/2C(=O)O)CC
  • 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) checkY
  • Key:MHWLWQUZZRMNGJ-UHFFFAOYSA-N checkY
  (verify)

Nalidixic acid (tradenames Nevigramon, NegGram, Wintomylon and WIN 18,320) is the first of the synthetic quinolone antibiotics.

In a technical sense, it is a naphthyridone, not a quinolone: its ring structure is a 1,8-naphthyridine nucleus that contains two nitrogen atoms, unlike quinoline, which has a single nitrogen atom.[1]

Synthetic quinolone antibiotics were discovered by George Lesher and coworkers as a byproduct of chloroquine manufacture in the 1960s;[2] nalidixic acid itself was used clinically, starting in 1967.

Nalidixic acid is effective primarily against Gram-negative bacteria, with minor anti-Gram-positive activity. In lower concentrations, it acts in a bacteriostatic manner; that is, it inhibits growth and reproduction. In higher concentrations, it is bactericidal, meaning that it kills bacteria instead of merely inhibiting their growth.

It has historically been used for treating urinary tract infections, caused, for example, by Escherichia coli, Proteus, Shigella, Enterobacter, and Klebsiella. It is no longer clinically used for this indication in the US as less toxic and more effective agents are available. The marketing authorization for nalidixic acid has been suspended throughout the EU.[3]

It is also a tool in studies as a regulation of bacterial division. It selectively and reversibly blocks DNA replication in susceptible bacteria. Nalidixic acid and related antibiotics inhibit a subunit of DNA gyrase and topoisomerase IV and induce formation of cleavage complexes.[4] It also inhibits the nicking-closing activity on the subunit of DNA gyrase that releases the positive binding stress on the supercoiled DNA.

  1. ^ Emmerson AM, Jones AM (May 2003). "The quinolones: decades of development and use". The Journal of Antimicrobial Chemotherapy. 51 (Suppl 1): 13–20. doi:10.1093/jac/dkg208. PMID 12702699.
  2. ^ Lesher GY, Froelich EJ, Gruett MD, Bailey JH, Brundage RP (September 1962). "1,8-Naphthyridine Derivatives. A New Class of Chemotherapeutic Agents". Journal of Medicinal and Pharmaceutical Chemistry. 5 (5): 1063–1065. doi:10.1021/jm01240a021. PMID 14056431.
  3. ^ "Disabling and potentially permanent side effects lead to suspension or restrictions of quinolone and fluoroquinolone antibiotics". European Medicines Agency. 11 March 2019.
  4. ^ Pommier Y, Leo E, Zhang H, Marchand C (May 2010). "DNA topoisomerases and their poisoning by anticancer and antibacterial drugs". Chemistry & Biology. 17 (5): 421–433. doi:10.1016/j.chembiol.2010.04.012. PMC 7316379. PMID 20534341.

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