新型白念珠菌生物被膜抑制剂IMB-H12的活性和作用机制研究  

The activity and mechanism of action of a novel Candida albicans biofilm inhibitor IMB-H12

作　　者：李丹 朱小红 卞聪 魏元娟 时文静 李妍 袁丽杰 LI Dan;ZHU Xiao-hong;BIAN Cong;WEI Yuan-juan;SHI Wen-jing;LI Yan;YUAN Li-jie(Hebei Key Laboratory for Chronic Diseases,Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases,School of Basic Medical Sciences,North China University of Science and Technology,Tangshan 063210,China;Beijing Key Laboratory of Antimicrobial Agents,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]华北理工大学基础医学院,河北省慢性疾病基础医学重点实验室,唐山市慢性病临床基础研究重点实验室,河北唐山063210 [2]中国医学科学院、北京协和医学院医药生物技术研究所,抗感染药物研究北京市重点实验室,北京100050

出　　处：《药学学报》2024年第4期948-956,共9页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(32141003);中国医学科学院医学与健康科技创新工程(2021-12M-1-070);河北省自然科学基金资助项目(H2021209027).

摘　　要：白念珠菌是真菌感染疾病中的主要病原菌,生物被膜的形成是白念珠菌毒力特征,同时也是重要的耐药机制,开发具有生物被膜抑制活性的抗真菌药物具有重要的意义。本研究对前期获得的新型的具有生物被膜抑制活性的化合物1-(cyclopentylamino)-3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propan-2-ol(简称IMB-H12)进行了深入的研究。IMB-H12对生物被膜的形成具有良好的抑制活性,并且对成熟的生物被膜具有一定的清除作用;初步作用机制研究发现IMB-H12能够抑制酵母-菌丝相的转换、抑制菌丝体的形成,降低白念珠菌的黏附活性和疏水性;IMB-H12能够诱导生物被膜菌细胞壁成分含量的改变,下调多个与黏附和菌丝形成相关的基因的表达。因此,对该化合物的进一步研究,有望发现新型的具有抗真菌活性的先导化合物。Candida albicans(C.albicans)stands as the primary opportunistic fungal pathogen responsible for fungal infections.The formation of biofilms constitutes a key virulence trait of C.albicans and a pivotal factor in drug resistance.Consequently,the development of antifungal drugs possessing biofilm inhibitory properties holds importance in the treatment of fungal infectious diseases.This study conducted in-depth research of the novel biofilm inhibitor named 1-(cyclopentylamino)-3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propan-2-ol(IMB-H12).IMB-H12 showed good inhibitory activity on the formation of biofilms and a certain scavenging effect on mature biofilms.Preliminary research on the mechanism of action has found that IMB-H12 can inhibit the transformation from yeast to hyphal phase,inhibit the formation of mycelium,and reduce the adhesion activity and hydrophobicity of Candida albicans.IMB-H12 could also induce changes in the content of cell wall components,downregulate the expression of multiple genes related to adhesion and hyphal formation.Therefore,further research on this compound is expected to discover new lead compounds with antifungal activity.

关 键 词：白念珠菌 生物被膜 1-(cyclopentylamino)-3-(4-(2 4 4-trimethylpentan-2-yl)phenoxy)propan-2-ol 黏附 菌丝 

分 类 号：R966[医药卫生—药理学]