title: In vitro and in vivo activities of the nitroimidazole CGI 17341 against Mycobacterium tuberculosis.
abstract: CGI 17341 (2-ethyl-5-nitro-2,3-dihydro[2-1b]imidazo-oxazole) is a novel orally active representative of the 5-nitroimidazole series of antimicrobial agents. At concentrations ranging from 0.1 to 0.3 micrograms/ml, CGI 17341 inhibited the drug-susceptible and multi-drug-resistant strains of Mycobacterium tuberculosis. CGI 17341 had no cross-resistance with isoniazid, rifampin, streptomycin, or ethambutol. While the in vitro activity of CGI 17341 against M. tuberculosis was comparable to those of isoniazid and rifampin, it was superior to those of streptomycin, ciprofloxacin or norfloxacin, and oxazolidinone DuP 721. The MIC of CGI 17341 was not affected when the pH of the medium was decreased from 6.8 to 5.6, while four- to sixfold increases in the MICs of ciprofloxacin and isoniazid were observed. In mice infected with M. tuberculosis, the 50% effective dose for CGI 17341 was 7.7 mg/kg of body weight (95% confidence limits, 3.5 and 10.27) when administered on days 11 and 12 postinfection. CGI 17341 gave a dose-dependent (r = 0.995) and significant increase in the survival time. Our data indicate that the 5-nitroimidazole CGI 17341 is a promising and novel antituberculosis compound with potent in vitro and in vivo activities. Further investigations on this compound are warranted.
authors.affiliation: Department of Microbiology and Infectious Diseases, Hindustan CIBA-GEIGY Pharmaceutical Research Center, Goregaon, Bombay, India.
authors.forename: D R
authors.initials: DR
authors.lastname: Ashtekar
authors.forename: R
authors.initials: R
authors.lastname: Costa-Perira
authors.forename: K
authors.initials: K
authors.lastname: Nagrajan
authors.forename: N
authors.initials: N
authors.lastname: Vishvanathan
authors.forename: A D
authors.initials: AD
authors.lastname: Bhatt
authors.forename: W
authors.initials: W
authors.lastname: Rittel
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001441:Bacteroides fragilis / Q000187:drug effects; D003470:Culture Media; D004352:Drug Resistance, Microbial; D005260:Female; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009593:Nitroimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D010080:Oxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D003470:Culture Media; D009593:Nitroimidazoles; D010080:Oxazoles; C080161:2-ethyl-5-nitro-2,3-dihydro(2-1b)imidazo-oxazole