查耳酮衍生物的合成及联合氟康唑抗耐药白色念珠菌活性

Synthesis and antifungal evaluation of chalcone derivatives combined with fluconazole against drug-resistant Candida albicans

摘要: 查耳酮是活性天然产物中常见的化学骨架，具有多种生物活性。设计合成了8个未见文献报道的含香豆素片段的查耳酮衍生物5a ~ 5h，其结构经¹H NMR和¹³C NMR确证。采用微量稀释法进行了体外联合氟康唑（fluconazole, FLC），抗耐药白色念珠菌作用评价。结果发现，该类化合物均具有协同FLC抗耐药白色念珠菌活性，特别是化合物5g与FLC联合用药的抗耐药白色念珠菌活性（MIC₅₀ = 5.60 μg/mL）远优于FLC单独用药的活性（MIC₅₀ = 200 μg/mL），可作为抗真菌药物增效剂。

Abstract: Chalcone is a common scaffold in natural products with optimal properties and biological activities.In this study, we designed and prepared eight new coumarin-chalcone derivatives (5a-5h), and confirmed their structures by ¹H NMR and ¹³C NMR. Their in vitro antifungal activity combined with fluconazole (FLC) against drug-resistant Candida albicans was tested by microdilution method.The results indicated that most chalcone derivatives showed good antifungal activity against drug resistant Candida albicans with FLC, particularly with compound 5g displaying better antifungal activity (MIC₅₀ = 5.60 μg/mL) than FLC (MIC₅₀ = 200 μg/mL) when combined with FLC, so, these derivatives could be used as synergists of antifungal drugs.