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Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis
Published on: June 13, 2021
Vasicine-Based Synergistic Antifungal Agents against FLC-Resistant Candida albicans Targeting Ras/cAMP/PKA Pathway
Di Zhao1,2, Wengang Wang2, Zhichang Xu2
1Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine, Kunming 650500, PR China.
Abstract:
A series of novel vasicine-based derivatives were designed and synthesized, and in vitro antifungal activities were evaluated. Most compounds showed synergistic antifungal effects with fluconazole (FLC) against FLC-resistant C. albicans. Compound 3n exhibited the best activity (MIC50 = 1.29 μM, FICI = 0.01) with no obvious cytotoxicity to 16HBE cells. Mechanistic studies revealed that 3n combined with FLC inhibited biofilm formation and efflux pump activity, and synergistically targeted the Ras/cAMP/PKA pathway to block yeast-to-hyphae transition. This dual mechanism provides a new strategy for treating FLC-resistant C. albicans infections.
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