Nitrate Esters of Heteroaromatic Compounds as Candida albicans CYP51 Enzyme Inhibitors

ChemMedChem. 2018 Feb 6;13(3):251-258. doi: 10.1002/cmdc.201700602. Epub 2018 Jan 26.


Four heteroaromatic compounds bearing nitrate esters were selected using a virtual-screening procedure as putative sterol 14α-demethylase (CYP51) Candida albicans inhibitors. Compounds were examined for their inhibition on C. albicans growth and biofilm formation as well as for their toxicity. NMR spectroscopy studies, in silico docking, and molecular dynamics simulations were used to investigate further the selectivity of these compounds to fungal CYP51. All compounds exhibited good antimicrobial properties, indicated with low minimal inhibitory concentrations and ability to inhibit formation of fungal biofilm. Moreover, all of the compounds had the ability to inhibit growth of C. albicans cells. N-(2-Nitrooxyethyl)-1Η-indole-2-carboxamide was the only compound with selectivity on C. albicans CYP51 that did not exhibit cytotoxic effect on cells isolated from liver and should be further investigated for selective application in new leads for the treatment of candidiasis.

Keywords: antimicrobial activity; biofilms; inhibitors; nitrate esters; virtual screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-alpha Demethylase Inhibitors / chemical synthesis*
  • 14-alpha Demethylase Inhibitors / pharmacology
  • 14-alpha Demethylase Inhibitors / toxicity
  • Amides / chemical synthesis*
  • Amides / pharmacology
  • Amides / toxicity
  • Animals
  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / pharmacology
  • Antifungal Agents / toxicity
  • Biofilms / drug effects
  • Candida albicans / enzymology*
  • Cell Line
  • Cell Survival / drug effects
  • Drug Design
  • Esters / chemistry*
  • Esters / pharmacology
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / pharmacology
  • Indoles / toxicity
  • Liver / cytology
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Protein Binding
  • Sterol 14-Demethylase / metabolism
  • Structure-Activity Relationship
  • Swine


  • 14-alpha Demethylase Inhibitors
  • Amides
  • Antifungal Agents
  • Esters
  • Indoles
  • Sterol 14-Demethylase