含丙基侧链的新型三唑类化合物的设计、合成和抗真菌活性研究  

Design,synthesis and antifungal activity of novel triazoles containing propyl side chains

作　　者：张海东 袁福淼 张大志 姜远英 俞世冲 ZHANG Haidong;YUAN Fumiao;ZHANG Dazhi;JIANG Yuanying;YU Shichong(School of Pharmacy,Naval Medical University,Shanghai 200433,China;Medical College,Tongji University,Shanghai 200092,China)

机构地区：[1]海军军医大学药学系,上海200433 [2]同济大学医学院,上海200092

出　　处：《药学实践与服务》2023年第2期86-90,共5页Journal of Pharmaceutical Practice and Service

基　　金：国家重点研究与发展计划(2021YFC2300400),国家自然科学基金(21202200,81830106)。

摘　　要：目的研究具有正丙基侧链和二取代苯环结构的三唑醇类化合物的抗真菌活性。方法设计合成了11个目标化合物;其结构通过1H NMR确证,部分化合物还通过13C NMR、高分辨质谱(HRMS)确证;选择3种真菌为实验菌株,根据美国国家临床实验室标准委员会(NCCLS)推荐的标准化抗真菌敏感性实验方法,进行体外抑菌活性测试。结果化合物B11对白念珠菌SC5314的活性较氟康唑更好,与泊沙康唑相当;化合物B10、B11、B4对新型隐球菌H99的活性较氟康唑更好,化合物B2、B3、B5、B6、B7对新型隐球菌H99的活性与氟康唑相当;所有化合物对烟曲霉菌活性欠佳。结论部分引入正丙基侧链和二取代苯基结构的目标化合物有一定抗真菌活性,可作为潜在的先导抗真菌药物。Objective To study the antifungal activity of a new series of triazole compounds with n-propyl side chain and disubstituted benzyl structure.Methods Eleven target compounds were designed and synthesized.The structures were confirmed by 1H NMR,and some compounds were confirmed by 13C NMR or HRMS.Three fungal strains were selected as experimental strains,and the antifungal activity was tested in vitro according to the standardized antifungal sensitivity test method recommended by National Committee for Clinical Laboratory Standards(NCCLS).Results Compound B11 showed better activity against candida albicans SC5314 than fluconazole and was comparable to posaconazole;Compounds B10,B11 and B4 showed better activity against cryptococcus neoformanis H99 than fluconazole,while compounds B2,B3,B5,B6 and B7 showed similar activity to fluconazole against cryptococcus neoformanis H99;while all compounds showed poor activity against aspergillus fumigatus.Conclusion Some of the target compounds with n-propyl side chain and disubstituted benzyl group structure had certain antifungal activity and could be identified as potential lead antifungal drugs.

关 键 词：三唑类衍生物 正丙基侧链 二取代苯基 合成 抗真菌活性 

分 类 号：R914.5[医药卫生—药物化学]