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Diarylacylhydrazones: Clostridium-Selective Antibacterials With Activity Against Stationary-Phase Cells, Chao Chen, Naveen K. Dolla, Gabriele Casadei, John B. Bremner, Kim Lewis, Michael J. Kelso
Diarylacylhydrazones: Clostridium-Selective Antibacterials With Activity Against Stationary-Phase Cells, Chao Chen, Naveen K. Dolla, Gabriele Casadei, John B. Bremner, Kim Lewis, Michael J. Kelso
Faculty of Science, Medicine and Health - Papers: part A
Current antibiotics for treating Clostridium difficile infections (CDI), that is, metronidazole, vancomycin and more recently fidaxomicin, are mostly effective but treatment failure and disease relapse remain as significant clinical problems. The shortcomings of these agents are attributed to their low selectivity for C. difficile over normal gut microflora and their ineffectiveness against C. difficile spores. This Letter reports that certain diarylacylhydrazones identified during a high-throughput screening/counter-screening campaign show selective activity against two Clostridium species (C. difficile and Clostridium perfringens) over common gut commensals. Representative examples are shown to possess activity similar to vancomycin against clinical C. difficile strains and to …