Bis‐Cyclic Guanidines as a Novel Class of Compounds Potent against Clostridium difficile,ChemMedChem

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Bis‐Cyclic Guanidines as a Novel Class of Compounds Potent against Clostridium difficile
ChemMedChem ( IF 3.6 ) Pub Date : 2018-06-14 , DOI: 10.1002/cmdc.201800240
Chunhui Li _{1,

2} , Peng Teng ₃ , Zhong Peng _{1,

4} , Peng Sang ₃ , Xingmin Sun ₁ , Jianfeng Cai ₃

Affiliation

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.

中文翻译：

双环胍是一类新型的对艰难梭菌有效的化合物

艰难梭菌感染（CDI）的症状范围从腹泻到严重的中毒性巨结肠甚至死亡。由于艰难梭菌迅速获得耐药性，被列为紧急的抗生素耐药性威胁，并已超过耐甲氧西林金黄色葡萄球菌（MRSA），成为美国最常见的医院获得性感染。为了对抗这种病原体，具有抗菌活性的新型伪肽结构类别可能发挥重要作用。在这里，我们报告了一组双环胍化合物，它们对艰难梭菌显示出有效的抗菌活性，并且具有良好的选择性。八种化合物显示出对艰难梭菌UK6的高体外效价，MIC值为1.0μgmL^-1，细胞毒性选择性指数（SI）最高可达37。此外，最具选择性的化合物在CDI小鼠模型中也可有效治疗艰难梭菌诱发的疾病，并且似乎是非常有希望的新候选药物用于治疗CDI。

更新日期：2018-06-14

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