3-甲基-4-氨基-5-巯基-1,2,4-三唑衍生物的合成及抗真菌活性

Synthesis and antifungal activity of 3-methyl-4-amino-5-mercapto-1,2,4-triazole derivatives

以3-甲基-4-氨基-5-巯基-1,2,4-三唑为起始原料,与卤代苄基在无水乙醇中回流制得中间体3-甲基-4-氨基-5-苄硫基-1,2,4-三唑,再与2,4-二氯苯甲醛在醋酸回流下缩合,即制得相应的目标化合物三唑席夫碱。利用1HNMR和元素分析确证了中间体和目标化合物的结构。选择7种真菌为实验菌株,对中间体和目标化合物进行体外抑菌活性测试。

The tanget compounds 3 were synthesized by the condensation between 2,4-dichlorobenzaldehyde and the intermediates （2） 3-methyl-4-amino-5-benzylsulfide-1,2,4-triazole which were produced from a reaction of the starting material 3-methyl-4- amino-5-mereapto-1,2,4-triazole and benzyl halide in an alcoholic medium. All intermediates 2 and target compounds 3 were confirmed by elemental analysis and 1^HNMR. MICs of all the title compounds were determined by using RPMI1640 test medium. The results of the preliminary antifungal test showed that all the title compounds exhibited potent antifungal activities against Can-dida albicans, Candida krusei, Candida parapsilosis, Candida glabrate, Cryptococcus neoformans and AspergiUus fumigatus to certain extents. MIC80 of compound 2i showed equal activity against Candida krusei to flucunazole. MIC80 of compound 3a showed equal activity against Candida parapsilosis to fluconazole and four times stronger than that of fluconazole against Candida glabrate. Compound 3j＇s MICs0 activity was 32 times, twice and four times stronger than that of fluconazole, terbinafme and itracozazole respectively against Candida glabrate in vitro.