Nalidixic acid
|
| Systematic (IUPAC) name |
| 1-Ethyl-7-methyl-4-oxo-[1,8]naphthyridine-3-carboxylic acid |
| Clinical data |
| AHFS/Drugs.com |
Consumer Drug Information |
| Pregnancy cat. |
B U.S. |
| Legal status |
Not FDA approved for clinical use in the United States |
| Routes |
Oral |
| Pharmacokinetic data |
| Protein binding |
90% |
| Metabolism |
Partially Hepatic |
| Half-life |
6-7 hours, significantly longer in renal impairment |
| Identifiers |
| CAS number |
389-08-2 Y |
| ATC code |
J01MB02 |
| PubChem |
CID 4421 |
| DrugBank |
DB00779 |
| ChemSpider |
4268 Y |
| UNII |
3B91HWA56M Y |
| KEGG |
D00183 Y |
| ChEBI |
CHEBI:100147 Y |
| ChEMBL |
CHEMBL5 Y |
| Chemical data |
| Formula |
C12H12N2O3 |
| Mol. mass |
232.235 g/mol |
SMILES
- O=C\2c1c(nc(cc1)C)N(/C=C/2C(=O)O)CC
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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) Y
Key:MHWLWQUZZRMNGJ-UHFFFAOYSA-N Y
|
| Y (what is this?) (verify) |
Nalidixic acid (tradenames Nevigramon, Neggram, Wintomylon and WIN 18,320) is the first of the synthetic quinolone antibiotics.
In the 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.[1] Used clinically from 1967.[1]
Nalidixic acid is effective against both gram-positive and gram-negative bacteria. 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 USA as less toxic and more effective agents are available.
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.[2] It also inhibits the nicking-closing activity on the subunit of DNA gyrase that releases the positive binding stress on the supercoiled DNA.
Contents
- 1 Adverse effects
- 2 Spectrum of bacterial susceptibility and resistance
- 3 References
- 4 External links
Adverse effects[edit]
Adverse effects include convulsions and hyperglycaemia.[3]
Spectrum of bacterial susceptibility and resistance[edit]
Aeromonas hydrophila, Clostridium and Haemophilus are generally susceptible to nalidixic acid, while other bacteria such as Bifidobacteria, Lactobacillus, Pseudomonas and Staphylococcus are resistant.[4]
References[edit]
- ^ a b c Emmerson, A. M.; Jones, A. M. (2003). "The Quinolones: Decades of Development and Use" (pdf). The Journal of Antimicrobial Chemotherapy 51 (Suppl 1): 13–20. doi:10.1093/jac/dkg208. PMID 12702699. edit
- ^ Pommier, Y., Leo, E., Zhang, H., Marchand, C. 2010. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem. Biol. 17: 421-433.
- ^ Fraser, A. G.; Harrower, A. D. (December 1977). "Convulsions and Hyperglycaemia Associated with Nalidixic Acid". British Medical Journal 2 (6101): 1518. doi:10.1136/bmj.2.6101.1518. PMC 1632822. PMID 589309.
- ^ "Nalidixic acid spectrum of bacterial susceptibility and Resistance" (pdf). Toku-E. 2011-09-14. Retrieved 2012-05-14.
External links[edit]
- MedlinePlus DrugInfo medmaster-a682042[dead link]
- "Nalidixic acid". HealthDigest.org.
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Antibacterials: nucleic acid inhibitors (J01E, J01M)
|
|
Antifolates
(inhibits
purine metabolism,
thereby inhibiting
DNA and RNA synthesis) |
| DHFR inhibitor |
- 2,4-Diaminopyrimidine
- Trimethoprim#
- Brodimoprim
- Tetroxoprim
- Iclaprim†
|
|
Sulfonamides
(DHPS inhibitor) |
Short-
acting |
- Sulfaisodimidine
- Sulfamethizole
- Sulfadimidine
- Sulfapyridine
- Sulfafurazole
- Sulfanilamide
- Sulfathiazole
- Sulfathiourea
|
|
Intermediate-
acting |
- Sulfamethoxazole
- Sulfadiazine#
- Sulfamoxole
|
|
Long-
acting |
- Sulfadimethoxine
- Sulfadoxine
- Sulfalene
- Sulfametomidine
- Sulfametoxydiazine
- Sulfamethoxypyridazine
- Sulfaperin
- Sulfamerazine
- Sulfaphenazole
- Sulfamazone
|
|
| Other/ungrouped |
- Sulfacetamide
- Sulfadicramide
- Sulfametrole
|
|
|
| Combinations |
- Trimethoprim/sulfamethoxazole#
|
|
|
Topoisomerase
inhibitors/
quinolones/
(inhibits
DNA replication) |
| 1st g. |
- Cinoxacin‡
- Flumequine
- Nalidixic acid
- Oxolinic acid
- Pipemidic acid
- Piromidic acid
- Rosoxacin
|
|
Fluoro-
quinolones |
| 2nd g. |
- Ciprofloxacin#
- Enoxacin‡
- Fleroxacin‡
- Lomefloxacin
- Nadifloxacin
- Ofloxacin
- Norfloxacin
- Pefloxacin
- Rufloxacin
|
|
| 3rd g. |
- Balofloxacin
- Grepafloxacin‡
- Levofloxacin
- Pazufloxacin
- Sparfloxacin‡
- Temafloxacin‡
- Tosufloxacin
|
|
| 4th g. |
- Besifloxacin
- Clinafloxacin†
- Garenoxacin
- Gemifloxacin
- Moxifloxacin
- Gatifloxacin‡
- Sitafloxacin
- Trovafloxacin‡/Alatrofloxacin‡
- Prulifloxacin
|
|
| Vet. |
- Danofloxacin
- Difloxacin
- Enrofloxacin
- Ibafloxacin
- Marbofloxacin
- Orbifloxacin
- Pradofloxacin
- Sarafloxacin
|
|
| Related (DG) |
- Aminocoumarins: Novobiocin
|
|
|
|
Anaerobic DNA
inhibitors |
| Nitro- imidazole derivatives |
- Metronidazole#
- Tinidazole
- Ornidazole
|
|
| Nitrofuran derivatives |
- Nitrofurantoin#
- Furazolidone‡
- Nifurtoinol
|
|
|
| RNA synthesis |
Rifamycins/
RNA polymerase |
- Rifampicin#
- Rifabutin
- Rifapentine
- Rifaximin
|
|
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
|
|
|
gr+f/gr+a (t)/gr-p (c)/gr-o
|
drug (J1p, w, n, m, vacc)
|
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