新型含喹啉和噻吩结构的抗真菌化合物的设计与合成  

Design and synthesis of novel antifungal compounds bearing quinoline and thiophene moieties

作　　者：庞磊[1,2] 赵晶[1,2] 倪廷峻弘[2] 臧成旭 丁子超 张大志[1,2] 姜远英[2] 

机构地区：[1]福建中医药大学药学院,福建福州350122 [2]第二军医大学药学院,上海200433

出　　处：《药学实践杂志》2017年第1期17-21,86,共6页Journal of Pharmaceutical Practice

基　　金：国家自然科学基金(81573473;21272270)

摘　　要：目的基于喹啉类和噻吩类抗真菌化合物的构效关系,设计合成含喹啉和噻吩结构片段的新型抗真菌化合物,并测试其对白念珠菌的抑制活性。方法以5-氰基噻吩-2-甲醛或者5-氰基噻吩-3-甲醛为起始原料,经还原氨化、氰基还原、与喹啉甲酸或异喹啉甲酸的酰胺化等反应,合成13个目标化合物,并通过1 H NMR和MS确证其化学结构,以微量液基稀释法测定这些化合物体外抗白念珠菌SC5314活性。结果目标化合物均具有一定的抗真菌活性,其中化合物6k显示很好的抗真菌活性,MIC80值为0.5μg/ml,与对照药氟康唑相当。结论所设计合成的含喹啉和噻吩结构片段的新型化合物具有较好的体外抗真菌活性,值得深入研究。Objective Based on the structure-activity relationships on the reported antifungal agents bearing quinoline or thiophene moieties, novel compounds bearing both quinoline and thiophene were designed, synthesized, and evaluated for in vitro antifungal activity against Candida albicans. Methods With 5-cyanothiophene-2-carbaldehyde or 5-cyanothiophene-3-car- baldehyde as starting materials, 13 compounds were synthesized via reductive amination, reduction of cyano group and amidation of quinoline-or isoquinoline-carboxylie acid. Their chemical structures were characterized by 1 H NMR and MS. In vitro antifungal screening against Candlda albicans SC5314 was performed with the microbroth dilution method. Results All the compounds exhibited potent antifungal activities against Candicla albicans. Among them, compound 6k showed the highest antifungal activity with MIC80 value of 0.5 μg/ml, which is same potent as fluconazole. Conclusion The designed compounds bearing both quinoline and thiophene exhibited potent antifungal activities, and deserve further research.

关 键 词：喹啉 抗真菌 噻吩 合成 白念珠菌 

分 类 号：R914.5[医药卫生—药物化学] R978.5[医药卫生—药学]