검색 상세

The Fluoroquinolone Compounds Potentiate the Antifungal Activity of the Echinocandins

플루오로퀴놀론 화합물들은 에키노칸딘의 항진균 활성을 증가시킨다

  • Jin-Ju Choi (최진주, 대학원 분자생명과학과 분자생물학전공)

초록/요약

The antifungal drugs of the echinocandins family showed high antifungal activity against Aspergillus fumigatus. However, it is necessary to improve the function of echinocandins because they have a paradoxical effect that restores growth at high concentrations of drugs and the emergence of fungi resistant to them. To find new chemical compounds that improve the paradoxical effect of echinocandins and potentiate the antifungal activity of echinocandins, a drug screening was performed using a chemical library consisting of 8,000 unique chemicals with 0.5 μg/ml of caspofungin. From the screening chemical library, it was found that 16 compounds of fluoroquinolone potentiate the antifungal activity of caspofungin. However, they have extremely low antifungal activity when treated alone against A. fumigatus. NE-E07, one of the fluoroquinolones screened, was found to potentiate the activity of the echinocandins but had no effect with other families of antifungal drugs such as voriconazole and amphotericin B. However, the known fluoroquinolone antibiotics that have fluoroquinolone structure failed to potentiate the activity of the echinocandins. In addition, NE-E07 potentiated the activity of caspofungin against the echinocandin-resistant strain USHM-M0051 isolated from the patients. Interestingly, NE-E07 did not potentiate the activity of echinocandins against Candida albicans and Cryptococcus neoformans, which are known fungal pathogens. Finally, co-treatment of NE-E07 and caspofungin decreased the ergosterol content of A. fumigatus compared to wild type and increased the viability of mice infected with A. fumigatus. These results indicate that NE-E07 has a unique synergistic function with echinocandins against A. fumigatus and provides a new paradigm for antifungal drugs.

more

목차

TABLE OF CONTENTS
ABSTRACT i
국문 초록 iii
TABLE OF CONTENTS vi
LIST OF TABLES viii
LIST OF FIGURES ix
CHAPTER 1. INTRODUCTION １
CHAPTER 2. MATERIALS AND METODS ５
2.1 Aspergillus strain, media, and conidia spore preparation ５
2.2 Antifungal activity assay ５
2.3 RNA sequence analysis ７
2.4 Ergosterol extraction and HPLC analysis ８
2.5 Mouse survival assay １０
CHAPTER 3. RESULTS １２
3.1 Some unique fluoroquinolone derivatives potentiate antifungal effect with caspofungin against A. fumigatus １２
3.2 NE-E07 potentiate the antifungal activity of caspofungin against the echinocandin-resistant strain of A. fumigatus USHM-M0051, but not against C. albicans or C. neoformans ２２
3.3 NE-E07 may have a similar mode of action to azole antifungal drug ３１
3.4 Co-administration of caspofungin and NE-E07 increases the survival rate of mice infected with A. fumigatus. ３８
CHAPTER 4. DISCUSSION ４２
REFERENCES ４７

more
반출 Meta View 목록