Synthesis and biological evaluation of hydrazone derivatives as antifungal agents

Molecules. 2015 May 20;20(5):9229-41. doi: 10.3390/molecules20059229.

Abstract

Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were obtained and their antifungal activity was evaluated against Candida species (C. parapsilosis, C. tropicalis, C. krusei, C. albicans, C. glabrata and C. lusitaneae) and Trichosporon asahii, in an in vitro screening. The minimum inhibitory concentrations (MICs) of the active compounds in the screening was determined against 10 clinical isolates of C. parapsilosis and 10 of T. asahii. The compounds 4-pyridin-2-ylbenzaldehyde] (13a) and tert-butyl-(2Z)-2-(3,4,5-trihydroxybenzylidine)hydrazine carboxylate (7b) showed the most promising MIC values in the range of 16-32 μg/mL and 8-16 μg/mL, respectively. The compounds' action on the stability of the cell membrane and cell wall was evaluated, which suggested the action of the compounds on the fungal cell membrane. Cell viability of leukocytes and an alkaline comet assay were performed to evaluate the cytotoxicity. Compound 13a was not cytotoxic at the active concentrations. These results support the discovery of promising candidates for the development of new antifungal agents.

Keywords: aldehydes; antifungal activity; emerging yeasts; hydrazones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Benzaldehydes / pharmacology
  • Candida / drug effects*
  • Candida / pathogenicity
  • Candidiasis / drug therapy
  • Carboxylic Acids / pharmacology
  • Cell Membrane / drug effects
  • Cell Survival / drug effects
  • Cell Wall / drug effects
  • Hydrazines / pharmacology
  • Hydrazones / chemical synthesis
  • Hydrazones / chemistry
  • Hydrazones / pharmacology*
  • Leukocytes / drug effects
  • Microbial Sensitivity Tests
  • Pyridines / pharmacology
  • Trichosporon / drug effects*
  • Trichosporon / pathogenicity
  • Trichosporonosis / drug therapy

Substances

  • 4-pyridin-2-ylbenzaldehyde
  • Antifungal Agents
  • Benzaldehydes
  • Carboxylic Acids
  • Hydrazines
  • Hydrazones
  • Pyridines
  • tert-butyl-(2Z)-2-(3,4,5-trihydroxybenzylidine)hydrazine carboxylate