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

FEBS J. 2011 Apr;278(7):1075-85. doi: 10.1111/j.1742-4658.2011.08021.x. Epub 2011 Feb 23.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Antifungal Agents / therapeutic use
  • Candida albicans / cytology
  • Candida albicans / drug effects*
  • Candida albicans / genetics*
  • Candida albicans / metabolism*
  • Candidiasis / drug therapy
  • Cell Respiration / drug effects
  • Drug Resistance, Fungal / drug effects
  • Electron Transport Complex I / drug effects
  • Electron Transport Complex I / physiology
  • Electron Transport Complex III / drug effects
  • Electron Transport Complex III / physiology
  • Gene Expression Profiling
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Microarray Analysis / methods*
  • Microbial Sensitivity Tests
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Molecular Structure
  • Reactive Oxygen Species / metabolism*
  • Tetrahydronaphthalenes / chemistry
  • Tetrahydronaphthalenes / pharmacology*
  • Tetrahydronaphthalenes / therapeutic use

Substances

  • 2-amino-nonyl-6-methoxyl-tetralin muriate
  • Antifungal Agents
  • Reactive Oxygen Species
  • Tetrahydronaphthalenes
  • Adenosine Triphosphate
  • Electron Transport Complex I
  • Electron Transport Complex III