新型2,5-二取代-1,3,4-二唑化合物的设计、合成及抗真菌活性

目的 研究新型2,5-二取代1,3,4-(噁)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-(噁)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0.25 μg/ml,与氟康唑(0.25 μg/ml)相当；化合物14、17对红色毛癣菌的MIC80值为0.25 μg/ml,是氟康唑(0.5 μg/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-(噁)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-(噁)二唑2位苯环上连有取代基对化合物的活性影响较大.

Design, synthesis and antifungal activity of novel 2,5-disubstituted 1,3,4-oxadiazoles

Objective To study the in vitro antifungal activity of novel 2,5-disubstituted 1,3,4-oxadiazoles.Methods Sixteen novel 2,5-disubstituted 1,3,4-oxadiazoles compounds have been designed,synthesized and characterized by 1HNMR,LC-MS spectra.Their antifungal activities were evaluated with six tested pathogenic fungi in vitro.Results All the title compounds exhibited potent antifungal activities against Candida albicans,Cryptococcus neoformans,Candida parapsilosis,Candida tropicalis,and Trichophyton rubrum,but not Aspergillus fumigatus.The activities of compound 14,17 and 18 against Candida atbicans and Cryptococcus neoformans(with the MIC80 0.25 μg/ml) were similar to that of fluconazole.The activities of compound 14 and 17 against Trichophyton rubrum(with the MIC80 0.25 μg/ml) were 2 times as high as that of fluconazole and were similar to that of ketoconazole.Conclusion The 1,2,3-triazole can be efficiently introduced to 1,3,4-oxadiazoles compounds by intermolecular 1,3-dipolar cycloaddition.All the title compounds exhibit certain antifungal activities with broad spectrum.The substituent of the benzene plays an important role in improving the antifungal activity of the compound.