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Antifungal Effects and Potential Mechanisms of Benserazide Hydrochloride Alone and in Combination with Fluconazole Against Candida albicans

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单位: [1]Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, People's Republic of China [2]Department of Pharmacy, China-Japan Friendship Hospital, Beijing, People's Republic of China [3]Department of Pharmacy, Shandong Second Provincial General Hospital, Jinan, People's Republic of China
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关键词: fluconazole-resistant Candida albicans benserazide fluconazole synergism biofilm Galleria mellonella

摘要:
Purpose: The resistance of C. albicans to traditional antifungal drugs brings a great challenge to clinical treatment. To overcome the resistance, developing antifungal agent sensitizers has attracted considerable attention. This study aimed to determine the anti-Candida activity of BEH alone or BEH-FLC combination and to explore the underlying mechanisms. Materials and Methods: In vitro antifungal effects were performed by broth microdilution assay and XTT reduction assay. Infected Galleria mellonella larvae model was used to determine the antifungal effects in vivo. Probes Fluo-3/AM, FITC-VAD-FMK and rhodamine 6G were used to study the influence of BEH and FLC on intracellular calcium concentration, metacaspase activity and drug efflux of C. albicans. Results: BEH alone exhibited obvious antifungal activities against C. albicans. BEH plus FLC not only showed synergistic effects against planktonic cells and preformed biofilms within 8 h but also enhanced the antifungal activity in infected G. mellonella larvae. Mechanistic studies indicated that antifungal effects of drugs might be associated with the increasement of calcium concentration, activation of metacaspase activity to reduce virulence and anti-biofilms, but were not related to drug efflux. Conclusion: BEH alone or combined with FLC displayed potent antifungal activity both in vitro and in vivo, and the underlying mechanisms were related to reduced virulence factors.

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出版当年[2020]版:
大类 | 3 区 医学
小类 | 3 区 药物化学 3 区 药学
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 药物化学 2 区 药学
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出版当年[2019]版:
Q2 CHEMISTRY, MEDICINAL Q2 PHARMACOLOGY & PHARMACY
最新[2023]版:
Q1 CHEMISTRY, MEDICINAL Q1 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均[2021-2025] 出版当年[2019版] 出版当年五年平均[2015-2019] 出版前一年[2018版] 出版后一年[2020版]

第一作者:
第一作者单位: [1]Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, People's Republic of China [2]Department of Pharmacy, China-Japan Friendship Hospital, Beijing, People's Republic of China
通讯作者:
通讯机构: [1]Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, People's Republic of China [3]Department of Pharmacy, Shandong Second Provincial General Hospital, Jinan, People's Republic of China [*1]Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jjinan, People's Republic of China
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