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.
Method: 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.
Conclusion: The results demonstrated that delicate manipulation of the NTZ core structure could lead to promising antimicrobial
agents against the nosocomial pathogens.