Nalidixic acid, the first synthetic and early-generation quinolone antibiotic, is used primarily for treatment of urinary tract infections caused by Escherichia coli and a few other Gram negative pathogens. Nalidixic acid reversibly inhibits DNA replication in susceptible Gram-negative bacteria by targeting DNA gyrase, which resolves topological constraints during DNA replication, and DNA topoisomerase IV, which resolves catenated DNA[1][2].
In vitro, Nalidixic acid exhibits potent antibacterial activity against Gram-negative bacteria, including Escherichia coli, Pasteurella spp., Klebsiella pneumoniae, Aerobacter aerogenes, Proteus spp., Salmonella spp., Shigella spp., and Brucella spp., with MIC values ranging from 0.5-32μg/mL, but shows weak activity against the Gram-positive bacteria Staphylococcus aureus and Diplococcus pneumoniae I, with MIC values of 50-100μg/mL and 250μg/mL, respectively[3].
In vivo, the acute toxicity (LD50) of Nalidixic acid in mice following oral and parenteral administration is: oral, 3300mg/kg; intravenous, 176mg/kg; and subcutaneous, 500mg/kg[3]. A single oral administration of Nalidixic acid treated systemic infections in mice caused by Escherichia coli, Aerobacter aerogenes, Proteus mirabilis, and Shigella spp., with ED50 values of 25mg/kg, 60mg/kg, 50mg/kg, and 62mg/kg, respectively[3].
References:
[1] Bisacchi, Gregory S. “Origins of the Quinolone Class of Antibacterials: An Expanded "Discovery Story".” Journal of medicinal chemistry vol. 58,12 (2015): 4874-82.
[2] Gutierrez A, Stokes JM, Matic I. Our Evolving Understanding of the Mechanism of Quinolones. Antibiotics (Basel). 2018;7(2):32.
[3] LESHER, G Y et al. “1,8-NAPHTHYRIDINE DERIVATIVES. A NEW CLASS OF CHEMOTHERAPEUTIC AGENTS.” Journal of medicinal and pharmaceutical chemistry vol. 5 (1962): 1063-5.