小G蛋白抑制剂CASIN的体外抗真菌活性研究  

Study on the antifungal activity of small G protein inhibitor CASIN in vitro

作　　者：巢雯 邓忠宇 郭士槿 郭熠凡 阎澜 邱丽娟 吕权真 CHAO Wen;DENG Zhongyu;GUO Shijin;GUO Yifan;YAN Lan;QIU Lijuan;LV Quanzhen(Basic Medicine School of Naval Medical University,Shanghai 200433,China;School of Pharmacy of Naval Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学基础医学院,上海200433 [2]海军军医大学药学院,上海200433

出　　处：《中国真菌学杂志》2022年第4期289-293,共5页Chinese Journal of Mycology

基　　金：国家自然科学基金(81902039)。

摘　　要：目的通过对小G蛋白抑制剂体外抗真菌活性的测定,筛选具有新结构类型的抗真菌活性化合物。方法采用微量液基稀释法考察不同小G蛋白抑制剂对于念珠菌的最低抑菌浓度(MIC),并从中筛选活性较强的化合物进一步进行抗真菌谱测定;采用时间-生长曲线和时间-杀菌曲线考察CASIN对于白念珠菌生长增殖的影响;采用菌丝诱导实验考察化合物CASIN对于白念珠菌菌丝形成的抑制效果;采用甲基四氮盐(XTT)法考察化合物CASIN对于白念珠菌生物被膜形成的抑制作用。结果在考察的小G蛋白抑制剂中,CASIN的体外抗真菌活性最强,对于近平滑念珠菌、克柔念珠菌、热带念珠菌、光滑念珠菌中均有较好的抑制作用,MIC为8~16μg/mL。16μg/mL CASIN可以有效抑制YPD培养基中白念珠菌的生长增殖,也在RPMI1640培养基中展现出对白念珠菌的杀菌活性;当培养基中CASIN浓度高于8μg/mL时,白念珠菌菌丝受到明显抑制;此外,8μg/mL的CASIN浓度对于白念珠菌的被膜生成具有80%以上的抑制率。结论小G蛋白抑制剂CASIN具有较强的体外抗念珠菌活性。Objective In order to find antifungal compounds with new structure,the antifungal activity of small G protein inhibitors were tested in vitro.Methods Micro-dilution method was used to investigate the minimum inhibitory concentration(MIC)of different small G protein inhibitors against Candida.After that,the more active compounds were selected for the further antifungal spectrum determination.Time-growth curves and time-kill curves were used to investigate the effect of CASIN on the growth and proliferation of Candida albicans.Hyphae formation experiment was used to investigate the inhibitory effect of compound CASIN on the formation of Candida albicans hyphae.XTT was used to investigate the inhibitory effect of compound CASIN on the formation of Candida albicans biofilms.Results Among the investigated small G protein inhibitors,CASIN had the strongest in vitro antifungal activity.It also had a good inhibitory effect on Candida parapsilosis,Candida krusei,Candida tropicalis,and Candida glabrata with the MIC of 8-16μg/mL.16μg/mL of CASIN could effectively inhibit the growth and proliferation of Candida albicans in YPD medium,and also exhibited fungicidal activity against Candida albicans in RPMI1640 medium.The hyphae formation of Candida albicans was significantly inhibited by 8μg/mL of CASIN.8μg/mL of CASIN had an inhibition rate of more than 80%for the biofilms formation of Candida albicans.Conclusion CASIN,a small G protein inhibitor,has strong antifungal activity in vitro.

关 键 词：小G蛋白 CASIN 抗真菌活性 

分 类 号：R978.5[医药卫生—药品]