2-Amino-nonyl-6-methoxyl-tetralin muriate activity against Candida albicans augments endogenous reactive oxygen species production - a microarray analysis study

• Published in: The FEBS journal Vol. 278; no. 7; pp. 1075 - 1085
• Main Authors: Liang, Rong Mei, Yong, Xiao Lan, Jiang, Yun Ping, Tan, Yong Hong, Dai, Bao Di, Wang, Shi Hua, Hu, Ting Ting, Chen, Xi, Li, Nan, Dong, Zhao Hui, Huang, Xiao Chun, Chen, Jun, Cao, Yong Bing, Jiang, Yuan Ying
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2011
• Subjects: 10b; action mechanism; adenosine triphosphate; Adenosine Triphosphate - metabolism; aerobiosis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antifungal Agents - therapeutic use; antifungal properties; antioxidants; ascorbic acid; Candida albicans; Candida albicans - cytology; Candida albicans - drug effects; Candida albicans - genetics; Candida albicans - metabolism; Candidiasis - drug therapy; Cell Respiration - drug effects; drug resistance; Drug Resistance, Fungal - drug effects; drugs; electron transfer; Electron Transport Complex I - drug effects; Electron Transport Complex I - physiology; Electron Transport Complex III - drug effects; Electron Transport Complex III - physiology; energy; Gene Expression Profiling; gene expression regulation; genes; Humans; mechanism of action; membrane potential; Membrane Potential, Mitochondrial - drug effects; microarray analysis; Microarray Analysis - methods; microarray technology; Microbial Sensitivity Tests; Mitochondria - drug effects; Mitochondria - metabolism; mitochondrial membrane; Molecular Structure; oligonucleotides; patients; reactive oxygen species; Reactive Oxygen Species - metabolism; ROS; Tetrahydronaphthalenes - chemistry; Tetrahydronaphthalenes - pharmacology; Tetrahydronaphthalenes - therapeutic use
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/j.1742-4658.2011.08021.x

Candida infections have become an increasingly significant problem, mainly because of the widespread nature of Candida and drug resistance. There is an urgent need to develop new classes of drugs for the treatment of opportunistic Candida infections, especially in medically complex patients. Previous studies have confirmed that 2-amino-nonyl-6-methoxyl-tetralin muriate (10b) possesses powerful antifungal activity in vitro against Candia albicans. To clarify the underlying action mechanism, an oligonucleotide microarray study was performed in C. albicans SC5314 without and with 10b treatment. The analytical results showed that energy metabolism-related genes, including glycolysis-related genes (PFK1, CDC19 and HXK2), fermentation-related genes (PDC11, ALD5 and ADH1) and respiratory electron transport chain-related genes (CBP3, COR1 and QCR8), were downregulated significantly. Functional analysis revealed that 10b treatment increased the generation of endogenous reactive oxygen species, and decreased mitochondrial membrane potential, ubiquinone-cytochrome c reductase (complex III) activity and intracellular ATP levels in C. albicans SC5314. Also, addition of the antioxidant ascorbic acid reduced the antifungal activity of 10b significantly. These results suggest that mitochondrial aerobic respiration shift and endogenous reactive oxygen species augmentation might contribute to the antifungal activity of 10b against C. albicans. This information may prove to be useful for the development of new strategies to treat Candida infections.