Bis‐Cyclic Guanidines as a Novel Class of Compounds Potent against Clostridium difficile |
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| Authors: | Dr Chunhui Li Dr Peng Teng Dr Zhong Peng Dr Peng Sang Prof Xingmin Sun Prof Jianfeng Cai |
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| Affiliation: | 1. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA;2. Department of Infection Control Center of Xiangya Hospital, Central South University, Changsha, China;3. Department of Chemistry, University of South Florida, Tampa, FL, USA;4. State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China |
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| Abstract: | Clostridium difficile infection (CDI) symptoms range from diarrhea to severe toxic megacolon and even death. Due to its rapid acquisition of resistance, C. difficile is listed as an urgent antibiotic‐resistant threat, and has surpassed methicillin‐resistant Staphylococcus aureus (MRSA) as the most common hospital‐acquired infection in the USA. To combat this pathogen, a new structural class of pseudo‐peptides that exhibit antimicrobial activities could play an important role. Herein we report a set of bis‐cyclic guanidine compounds that show potent antibacterial activity against C. difficile with decent selectivity. Eight compounds showed high in vitro potency against C. difficile UK6 with MIC values of 1.0 μg mL?1, and cytotoxic selectivity index (SI) values up to 37. Moreover, the most selective compound is also effective in the treatment of C. difficile‐induced disease in a mouse model of CDI, and appears to be a very promising new candidate for the treatment of CDI. |
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| Keywords: | antibiotics bis-cyclic guanidines Clostridium difficile drug resistance |
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