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Due to its rapid acquisition of resistance, <jats:italic>C.\u2005difficile<\/jats:italic> is listed as an urgent antibiotic\u2010resistant threat, and has surpassed methicillin\u2010resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) as the most common hospital\u2010acquired infection in the USA. To combat this pathogen, a new structural class of pseudo\u2010peptides that exhibit antimicrobial activities could play an important role. Herein we report a set of bis\u2010cyclic guanidine compounds that show potent antibacterial activity against <jats:italic>C.\u2005difficile<\/jats:italic> with decent selectivity. Eight compounds showed high in vitro potency against <jats:italic>C.\u2005difficile<\/jats:italic> UK6 with MIC values of 1.0\u2005\u03bcg\u2009mL<jats:sup>\u22121<\/jats:sup>, and cytotoxic selectivity index (SI) values up to 37. Moreover, the most selective compound is also effective in the treatment of <jats:italic>C.\u2005difficile<\/jats:italic>\u2010induced disease in a mouse model of CDI, and appears to be a very promising new candidate for the treatment of CDI.<\/jats:p>","DOI":"10.1002\/cmdc.201800240","type":"journal-article","created":{"date-parts":[[2018,5,16]],"date-time":"2018-05-16T15:20:20Z","timestamp":1526484020000},"page":"1414-1420","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Bis\u2010Cyclic Guanidines as a Novel Class of Compounds Potent against <i>Clostridium difficile<\/i>"],"prefix":"10.1002","volume":"13","author":[{"given":"Chunhui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Morsani College of Medicine University of South Florida  12901 Bruce B. Downs Boulevard Tampa FL 33612 USA"},{"name":"Department of Infection Control Center of Xiangya Hospital Central South University  Changsha 410008 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7412-9646","authenticated-orcid":false,"given":"Peng","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of South Florida  4202 E. Fowler Avenue Tampa FL 33620 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Morsani College of Medicine University of South Florida  12901 Bruce B. 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