3-取代三唑类抗真菌化合物的设计、合成及体外抗真菌活性

Design,synthesis,and antifungal activity of 3-substituted triazole derivatives

目的合成1,2,3-三唑侧链取代三唑醇类化合物并考察其体外抗真菌活性。方法设计合成了21个三唑醇类新化合物,所得化合物结构都经过1HNMR、MS确证;选择8种真菌为实验菌株,进行体外抗真菌活性测试。结果所合成的化合物均具有一定的体外抗真菌活性,其中化合物7{1-(1H-1,2,4-三唑-1-基)-2-(2,4二氟苯基)-3-[N,N-(4-亚甲基-1-取代苄基-1H-1,2,3三唑)]-2-丙醇}对白色念珠菌的MIC80值为0.25μg/ml,是氟康唑活性的4倍,化合物Ⅵ{1-(1H-1,2,4-三唑-1-基)-2-(2,4二氟苯基)-3-(N,N-二炔丙基)-2-丙醇}对白色念珠菌的MIC80值为0.0156μg/ml,是氟康唑活性的64倍,是伊曲康唑的4倍。结论利用13偶极加成反应可以方便地在化合物中引入1,2,3-三唑基;较大的侧链结构可能不利于目标化合物活性的提高。

Objective To study the in vitro antifungal activity of triazole alcohols by introduction of 1,2,3-triazole as the side chain.Methods Twenty-one novel triazole alcohol compounds were designed,synthesized,and characterized by 1 HNMR and MS spectra.The in vitro antifungal activities of the compounds were evaluated using eight kinds of pathogenic fungi.Results All the synthesized compounds exhibited certain antifungal activities.The MIC80value of compound7 1-（1 H-1,2,4-triazole-1-yl）-2-（2,4-difluorophenyl）-3-[N,N-（1-substituted-benzyl-4-methylene-1 H-1,2,3-triazole）]against Candida albicans was 0.25μg/ml,with its activity being 4times that of fluconazole.The MIC80value of compoundⅥ1-（1 H-1,2,4-triazole-1-yl）-2-（2,4-difluorophenyl）-3-（N,N-dipropargyl）-2-propanols against Candida albicans was 0.015 6μg/ml,with its activity being 64times that of fluconazole and 4times that of itraconazole.Conclusion The 1,2,3-triazole can be efficiently introduced by intermolecular 1,3-dipolar cycloaddition.Large side chains may be a disadvantage for improving the antifungal activity of the title compounds.