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Updated: Jul 15, 2026
09:44
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.
ACS Medicinal Chemistry Letters
|July 14, 2026
Summary
Novel vasicine derivatives combat fluconazole-resistant Candida albicans. Compound 3n shows potent synergistic antifungal activity by inhibiting biofilm and targeting key cellular pathways.
Area of Science:
- Medicinal Chemistry
- Antimicrobial Resistance
- Molecular Biology
Background:
- Fluconazole (FLC)-resistant Candida albicans poses a significant clinical challenge.
- Development of novel antifungal agents with unique mechanisms is crucial.
Purpose of the Study:
- To design and synthesize novel vasicine-based derivatives.
- To evaluate their in vitro antifungal activity, particularly against FLC-resistant C. albicans.
- To elucidate the mechanism of action for promising compounds.
Main Methods:
- Synthesis of vasicine derivatives.
- In vitro antifungal activity testing (MIC50, FICI) against C. albicans.
- Cytotoxicity assessment using 16HBE cells.
- Mechanistic studies including biofilm inhibition, efflux pump activity assay, and pathway analysis (Ras/cAMP/PKA).
Main Results:
- Several vasicine derivatives demonstrated synergistic antifungal effects with FLC against FLC-resistant C. albicans.
- Compound 3n exhibited potent activity (MIC50 = 1.29 μM, FICI = 0.01) with no significant cytotoxicity.
- Compound 3n, in combination with FLC, inhibited biofilm formation and efflux pump activity.
- Mechanistic studies indicated synergistic targeting of the Ras/cAMP/PKA pathway to block yeast-to-hyphae transition.
Conclusions:
- Vasicine derivatives, especially compound 3n, represent a promising strategy against FLC-resistant C. albicans.
- The dual mechanism of inhibiting biofilm and targeting the Ras/cAMP/PKA pathway offers a novel therapeutic approach.
- This research provides a foundation for developing new treatments for challenging C. albicans infections.
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