posted on 2023-11-17, 15:36authored byLiping Li, Hao Wu, Jiayin Wang, Zhe Ji, Ting Fang, Hui Lu, Lan Yan, Fuming Shen, Dazhi Zhang, Yuanying Jiang, Tingjunhong Ni
Fungal
pathogens can cause life-threatening infections, yet current
antifungals are inadequate at treating many of these, highlighting
the importance of novel drug discovery. Here, we report hit compound L14, a novel 8-hydroxyquinoline derivative with potent and
broad-spectrum antifungal activity. In vitro experiments
exhibited that L14 had better activity and lower cytotoxicity
than that of clioquinol and showed synergy in combination with fluconazole
(FLC). In a Candida albicans-infected
murine model, L14 at 2 mg/kg showed better in
vivo efficacy than clioquinol at reducing fungal burden and
extending the survival of C. albicans-infected mice. In addition, L14 alone or in combination
with FLC had significant inhibitory activity against hypha and biofilm
formation. Overall, our data indicated that 8-hydroxyquinoline derivative L14 has favorable pharmacokinetics and acceptable safety profiles
and could be further investigated as a promising antifungal hit compound.