Nalidixic acid is credited to be the first quinolone synthesized in laboratory in 1962. Its chemical structure is shown in Fig. 45.16. It is a broad spectrum chemotherapeutic agent and is useful against gram-negative bacteria (causing urinary tract infection) and some gram-positive ones. Nalidixic acid is bactericidal and is effective when administered orally.
This antibiotic sometimes causes side effects, particularly gastro-intestinal upset. More recently a family of fluoroquinolone derivatives of nalidixic acid such as ciprofloxacin, norfloxacin, and ofloxacin has been produced and are routinely used to treat urinary tract infections, gonorrhoea, chlamydial infections, and intestinal diseases in humans.
Ciprofloxacin is also the drug of choice for treating infections from penicillin-resistant strains of Bacillus anthracis, the cause of anthrax. Fluoroquinolones are also used extensively in the beef and poultry industries for prevention and treatment of respiratory diseases.
The mechanism of action of nalidixic acid is related to DNA gyrase inhibition as nalidixic acid, like some other quinolones, acts by inhibiting the bacterial DNA gyrase. This enzyme introduces negative twists in DNA and helps separate its strands. DNA gyrase inhibition disrupts DNA replication and repair, transcription, bacterial chromosome separation during division, and other cellular activities involving DNA.