Therapeutic activities of nitrothiazole derivatives in experimental infections with Salmonella typhimurium and Bacteroides fragilis.
The antibacterial activities of niridazole (AmbilharR) and 12 other newly synthesized nitrothiazole derivatives were examined. Most of these compounds were active in vitro against Salmonella typhimurium (MICs 1-4 mg/l) and Bacteroides fragilis (MICs 0.015-0.03 mg/l). A therapeutic effect as determined by a reduction of bacterial counts per spleen of mice infected with Salm. typhimurium could only be achieved with those agents which displayed a similar side chain as niridazole, i.e. an imidazolidinone ring. Other nitrothiazole derivatives with a cleaved imidazolidinone ring as the side chain, although active in vitro, could not exert a reduction of bacterial counts in vivo. Similar results were obtained in mice infected with Bact. fragilis. Whereas niridazole and another nitrothiazole derivative with an imidazolidinone ring in the side chain were able to reduce the bacterial counts in a subcutaneous abscess, the derivative with a laminar side chain was inactive in vivo, although highly active in vitro.
D000038:Abscess / Q000188:drug therapy / Q000382:microbiology; D000818:Animals; D001442:Bacteroides Infections / Q000188:drug therapy* / Q000382:microbiology; D001441:Bacteroides fragilis / Q000187:drug effects; D005260:Female; D051379:Mice; D008826:Microbial Sensitivity Tests; D009560:Niridazole / Q000494:pharmacology / Q000627:therapeutic use*; D012481:Salmonella Infections, Animal / Q000188:drug therapy* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000187:drug effects; D013154:Spleen / Q000382:microbiology; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*
D013844:Thiazoles; D009560:Niridazole