Study on antifungal activity and mechanism of 2-aryl-4-substituted quinoline compound
GUO Zhongjie
ZHANG Rong
ZHAO Mei
ZHANG Shaohua
LIU Wei
LI Muqiong
JIANG Ru
WANG Shengzheng
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.
Keywords：antifungal activityintracellular reactive oxygen speciesfungicidal activity
Publication Date：2023-12-28
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：7( 1164-1169,1176 )