The Anti- Candida albicans Agent 4-AN Inhibits Multiple Protein Kinases

Molecules. 2019 Jan 2;24(1):153. doi: 10.3390/molecules24010153.

Abstract

Small molecules containing quinone and/or oxime moieties have been found as promising anti-fungal agents. One of them is 4-AN, a recently reported potent anti-Candida compound, which inhibits the formation of hyphae, decreases the level of cellular phosphoproteome, and finally shows no toxicity towards human erythrocytes and zebrafish embryos. Here, further research on 4-AN is presented. The results revealed that the compound: (i) Kills Candida clinical isolates, including these with developed antibiotic resistance, (ii) affects mature biofilm, and (iii) moderately disrupts membrane permeability. Atomic force microscopy studies revealed a slight influence of 4-AN on the cell surface architecture. 4-AN was also shown to inhibit multiple various protein kinases, a characteristic shared by most of the ATP-competitive inhibitors. The presented compound can be used in novel strategies in the fight against candidiasis, and reversible protein phosphorylation should be taken into consideration as a target in designing these strategies.

Keywords: 4-AN; Candida albicans; antifungal agent; arylcyanomethylenequinones; atomic force microscopy; protein kinases.

MeSH terms

  • Antifungal Agents / pharmacology*
  • Biofilms / drug effects
  • Biological Transport
  • Candida albicans / drug effects*
  • Cell Membrane
  • Drug Evaluation, Preclinical
  • Drug Resistance, Microbial
  • Humans
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Oximes / therapeutic use*
  • Phosphorylation
  • Protein Binding
  • Protein Kinase Inhibitors / pharmacology*
  • Quinones / therapeutic use*
  • Surface Properties

Substances

  • Antifungal Agents
  • Oximes
  • Protein Kinase Inhibitors
  • Quinones