Fluoroquinolone derivatives have a synergistic effect on the antifungal activity of echinocandins in Aspergillus fumigatus

Abstract

Abstract The antifungal drugs of the echinocandins family showed high antifungal activity against A. fumigatus. However, echinocandins have a paradoxical effect and it is necessary to improve the paradoxical effect of echinocandins. To develop a new antifungal drug that improves the paradoxical effect of echinocandins, we performed a drug screening using a chemical library consisting of 8,000 unique chemicals with 0.5µg/ml of caspofungin. From the screening chemical library, we found that fluoroquinolone compounds activate the antifungal activity of caspofungin and no paradoxical effect of echinocandins was detected. 50 chemicals from the chemical library had a synergistic effect on the antifungal activity of caspofungin and among them, 16 compounds were fluoroquinolone derivative compounds with low antifungal activity when treated alone against A. fumigatus. NE-E07, which is one of the fluoroquinolone compounds we screened, showed a synergistic effect with all kinds of the echinocandins antifungal drugs, but no synergistic effect with other families of antifungal drugs such as voriconazole and amphotericin B. Furthermore, the quinolone antibiotics, which have a fluoroquinolone structure, did not show any synergistic effect with caspofungin. Finally, co-treatment of NE-E07 and caspofungin increased the viability of mice infected with A. fumigatus. These results indicate that the fluoroquinolone compounds we screened have a unique function of antifungal drugs and provide a new paradigm for antifungal drugs.