title: Nitazoxanide Analogues as Antimicrobial Agents Against Nosocomial Pathogens.
abstract: BACKGROUND
  The frequent use of antibacterial agents and the exposure of the patients to lifesaving intervention processes are consistently associated with the increased chance of nosocomial infections and the emergence of multidrug resistant microorganisms in the hospital environment. Thus, new antimicrobial agents are of unmet need to treat the severe nosocomial infections caused by these putative pathogens resistant to currently available agents.
  
  
  METHODS
  Design, synthesis, and biological evaluation of analogues of nitazoxanide (NTZ), an FDA approved thiazolide antiparasitic, as new antimicrobial agents against nosocomial pathogens were described. The NTZ analogues were rationally explored on the basis of either increasing the electronic resonance effects at the nitrothiazolide moiety or improving the anionic form of the whole NTZ structure.
  
  
  RESULTS
  The MICs and MBCs values of these NTZ analogues against prevalent nosocomial pathogens were measured. The benzologous analogues 3a and 4a and p-chlorobenzenesulfonamides 8d and 9d exhibited tremendous antimicrobial activities, which were 100- to 2000-fold more potent than NTZ and ciprofloxacin.
  
  
  CONCLUSIONS
  The results demonstrated that delicate manipulation of the NTZ core structure could lead to promising antimicrobial agents against the nosocomial pathogens.
authors.forename: Jia-Suey
authors.initials: JS
authors.lastname: Gau
authors.forename: Wen-Pao
authors.initials: WP
authors.lastname: Lin
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Kuo
authors.affiliation: School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan. hmk@ndmctsgh.edu.tw.
authors.forename: Ming-Kuan
authors.initials: MK
authors.lastname: Hu
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D003428:Cross Infection / Q000382:microbiology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D016937:Gram-Positive Endospore-Forming Rods / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009574:Nitro Compounds; D010797:Phthalimides / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D009574:Nitro Compounds; D010797:Phthalimides; D013449:Sulfonamides; D013844:Thiazoles; D002939:Ciprofloxacin; C041747:nitazoxanide