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

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.