Optimization and antifungal activity of quinoline derivatives linked to chalcone moiety combined with FLC against Candida albicans

In present work, a series of quinoline derivatives linked to chalcone moiety have been prepared, and their in vitro and in vivo antifungal activities against C. albicans have been evaluated. The results indicated that quinoline combined with fluconazole (FLC) showed good inhibitory activity against C. albicans. Especially, compound PK10 combined with FLC displayed the best antifungal activity against 14 FLC-resistant C. albicans strains with almost no cytotoxicity. Preliminary mechanistic studies proved that PK-10 combined with FLC could inhibit the hyphae formation of C. albicans, induce the accumulation of reactive oxygen species (ROS), the damage of mitochondrial membrane potential and the decrease of intracellular ATP content, which led to mitochondrial dysfunction. In vivo studies found obvious effects of the co-treatment regimen had obvious effects based on histological analysis, body weight curves, and coefficients of major organs. Therefore, the optimization of quinolone-chalcone derivatives combined with FLC could exert the potent antifungal activity in vitro and in vivo obviously, suggesting them as new agents to treat drug-resistant C. albicans infection.

Automated summary

A series of quinoline derivatives linked to chalcone moiety were prepared and their antifungal activities against C. albicans were evaluated. Quinoline combined with fluconazole (FLC) showed good inhibitory activity and compound PK10 displayed the best antifungal activity against FLC-resistant strains. Mechanistic studies revealed that PK-10 combined with FLC inhibited hyphae formation, induced accumulation of reactive oxygen species, mitochondrial dysfunction, and decreased ATP content. In vivo studies confirmed the effectiveness of the combination treatment based on histological analysis, body weight curves, and organ coefficients.