论文部分内容阅读
目的研究新型2,5-二取代1,3,4-二唑化合物的体外抗真菌活性。方法设计合成了16个新型2,5-二取代-1,3,4-二唑化合物,所得化合物都经过1HNMR、LC-MS确证;选择6种真菌为实验菌株,进行体外抗真菌活性测试。结果所合成的目标化合物对除熏烟曲霉菌外的所有菌株(白假丝酵母菌、新生隐球菌、热带假丝酵母菌、近平滑假丝酵母菌、红色毛癣菌)均具有一定的体外抗真菌活性,其中化合物14、17、18对白假丝酵母菌和新生隐球菌的MIC80值均为0.25μg/ml,与氟康唑(0.25μg/ml)相当;化合物14、17对红色毛癣菌的MIC80值为0.25μg/ml,是氟康唑(0.5μg/ml)的2倍,与酮康唑相当。结论利用1∶3偶极加成反应可在1,3,4-二唑化合物的5-位引入1,2,3-三唑取代基。初步体外活性显示,所合成的目标化合物对除熏烟曲霉菌外的所有菌株均具有一定的体外抗真菌活性。1,3,4-二唑2-位苯环上连有取代基对化合物的活性影响较大。
Aim To study the in vitro antifungal activity of 2,5-disubstituted 1,3,4-oxadiazole compounds. Methods Sixteen novel 2,5-disubstituted-1,3,4-oxadiazole compounds were designed and synthesized. All the compounds were confirmed by 1HNMR and LC-MS. Six kinds of fungi were selected as experimental strains to test the antifungal activity in vitro. Results The synthesized target compounds had certain in vitro activities against all strains except A. fumigatus (Candida albicans, Cryptococcus neoformans, Candida tropicalis, Candida parapsilosis and Trichophyton rubrum) Antifungal activity. The MIC80 values of compound 14, 17, 18 against Candida albicans and Cryptococcus neoformans were all 0.25μg / ml, which was equivalent to that of fluconazole (0.25μg / ml) The MIC80 value of bacteria was 0.25 μg / ml, which was twice that of fluconazole (0.5 μg / ml), comparable to that of ketoconazole. Conclusion The 1, 3-triazole substituent can be introduced into the 5-position of 1,3,4-oxadiazole by 1: 3 dipolar addition reaction. The preliminary in vitro activity showed that the synthesized target compounds had certain antifungal activity in vitro against all strains except Aspergillus fumigatus. 1,3,4-oxadiazole 2-position benzene ring with substituents on the activity of compounds.