8-羟基喹啉衍生物作为潜在的艰难梭菌抗生素的设计、合成和活性评价

Design,synthesis and biological evaluation of 8-hydroxyquinoline derivatives as potential clostridium difficile antibiotics

目的 艰难梭菌感染(CDI)目前治疗措施主要包括抗生素疗法、粪菌移植疗法等,其治疗后存在较高的复发率,需寻求一种更有效的替代疗法。方法 本研究基于有前景的8-羟基喹啉骨架,设计、合成了一系列8-羟基喹啉衍生物。结果 针对艰难梭菌的活性测试表明,多数分子对艰难梭菌具有良好的抑菌作用,其中化合物6f显示出较强的杀伤艰难梭菌活性。结论 本研究发现了新型具有抗艰难梭菌的8-羟基喹啉衍生物,可作为良好的先导化合物进一步研发。

Objective To find a more effective alternative therapy for antibiotic therapy and fecal microbiota transplantation in current primary treatment of clostridioides difficile infection(CDI)because of the high recurrence rate.Methods A series of 8-hydroxyquinoline derivatives were designed and synthesized based on 8-hydroxyquinoline scarffold.Results The activity test against C.difficile showed that most of the molecules exhibited good antibacterial activity against C.difficile,and compound 6f showed attractive anti-C.difficile activity.Conclusion A new type of 8-hydroxyquinoline derivatives with anti-clostridium difficile was found,which could be used as good lead compounds for further development.