空军军医大学学报2023，Vol.44Issue(12)：1164-1169,1176,7.DOI:10.13276/j.issn.2097-1656.2023.12.005
2-芳基-4-取代喹啉类化合物的抗真菌活性和作用机制研究
Study on antifungal activity and mechanism of 2-aryl-4-substituted quinoline compound
摘要
Abstract
Objective To develop new antifungal drugs to solve the clinical problems of high morbidity and mortality of deep fungal infections and resistance of antifungal drugs.Methods The antifungal susceptibility testing was used to screen the activity of the in-house compound library,and the antifungal spectrum of the positive compounds was evaluated by a broth microdilution method.The effects of positive compounds on fungal survival were evaluated by growth experiments and time-kill assay.The effect of compounds on mycelium formation was observed by inverted microscope.The effects of compounds on reactive oxygen species(ROS)production,biofilm permeability and apoptosis were detected by flow cytometry.Results The 2-aryl-4-substituted quinoline compound J6 had the best antifungal activity,with minimum inhibitory concentration of 18.9,18.9,37.8,and 37.8 mg/L against Candida albicans,Candida tropicalis,Candida krusei and Cryptococcus neoformans,respectively.J6 significantly inhibited the growth of these four fungi,and it even showed fungicidal activity against Cryptococcus neoformans.Additionally,J6 could also suppress hyphal formation.Studies on the mechanism of action revealed that J6 increased the membrane permeability of fungal cells and intracellular ROS level,thus inducing the apoptosis of fungal cells.Conclusion The 2-aryl-4-substituted quinoline compound J6 displayed promising antifungal activity.Further study on its structural optimization and mechanism is expected to discover novel antifungal agents.关键词
抗真菌活性/细胞内活性氧/杀真菌活性Key words
antifungal activity/intracellular reactive oxygen species/fungicidal activity分类
医药卫生引用本文复制引用
过忠杰,张蓉,赵玫,张邵华,刘伟,李穆琼,姜茹,王胜正..2-芳基-4-取代喹啉类化合物的抗真菌活性和作用机制研究[J].空军军医大学学报,2023,44(12):1164-1169,1176,7.基金项目
陕西省自然科学基金面上项目(2022JM-498) （2022JM-498）
空军军医大学军事医学提升计划项目(2021JSTS07) （2021JSTS07）
