Antifungal Activity and Multi-Target Mechanism of Action of Methylaervine on Candida albicans .

Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, c1995-

Candida albicans*/drug effects ; Candida albicans*/growth & development ; Antifungal Agents*/pharmacology ; Antifungal Agents*/chemistry ; Biofilms*/drug effects ; Microbial Sensitivity Tests*; Carbolines/pharmacology ; Carbolines/chemistry ; Cell Membrane/drug effects

The discovery of a lead compound against Candida albicans is urgently needed because of the lack of clinically available antifungal drugs and the increase in drug resistance. Herein, a β -carboline alkaloid methylaervine (MET) exhibited potential activity against C. albicans (MIC = 16-128 μg/mL), no hemolytic toxicity, and a low tendency to induce drug resistance. An antifungal mechanism study indicated that MET effectively inhibited the biofilm formation and disrupted the mature biofilm. Moreover, filamentation formation and spore germination were also weakened. The electron microscopy analysis revealed that MET could damage the cell structure, including the cell wall, membrane, and cytoplasm. In particular, the permeability and integrity of the cell membrane were destroyed. When it entered the fungi cell, it interfered with the redox homeostasis and DNA function. Overall, MET can inhibit the growth of C. albicans from multiple channels, such as biofilm, filamentation, cell structure, and intracellular targets, which are difficult to mutate at the same time to generate drug resistance. This work provides a promising lead compound for the creation of new antifungal agents against C. albicans .

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2023HWYQ-096 Natural Science Foundation of Shandong Province; 2023YJSCX006 Graduate Student Research Grant from Shandong Second Medical University; 2023GX022, 2023GX035 Weifang Science and Technology Development Plan for 2021

Keywords: Candida albicans; antifungal; methylaervine; multi-target mechanism of action

0 (Antifungal Agents)
0 (Carbolines)

Date Created: 20240928 Date Completed: 20240928 Latest Revision: 20240930

20240930

PMC11433846

10.3390/molecules29184303

39339297