Differential inhibition of Candida albicans CYP51 with azole antifungal stereoisomers

FEMS Microbiol Lett. 1997 Apr 1;149(1):25-30. doi: 10.1111/j.1574-6968.1997.tb10303.x.


Azole antifungal compounds are important in agriculture and in the treatment of mycotic infection. The target enzyme, sterol 14 alpha-demethylase (CYP51), is inhibited through binding of triazole N-4 to the haem of this P450, as a sixth ligand together with the N-1 substituent groups interacting in some way with the apoprotein. Here we use Saccharomyces cerevisiae expression systems for the target enzyme of Candida albicans to investigate binding of enantiomers of the azole antifungal compounds SCH39304 and tetraconazole. A molecular model produced previously provided qualitative explanations for these differences. Interaction of the azole antifungal aromatic group with Phe-233 or -235 may cause the higher activity for (R)-tetraconazole while inactivity of the (SS)-enantiomer of SCH39304 was predicted to result from incompatibility of the hydrophilic sulfonyl moiety when located into the hydrophobic pocket of the active site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Binding Sites / physiology
  • Candida albicans / drug effects*
  • Candida albicans / enzymology
  • Chlorobenzenes / chemistry
  • Chlorobenzenes / pharmacology*
  • Cytochrome P-450 Enzyme Inhibitors*
  • Enzyme Inhibitors / pharmacology
  • Fungal Proteins / antagonists & inhibitors
  • Oxidoreductases / antagonists & inhibitors*
  • Stereoisomerism
  • Sterol 14-Demethylase
  • Triazoles / chemistry
  • Triazoles / pharmacology*


  • Antifungal Agents
  • Chlorobenzenes
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Fungal Proteins
  • Triazoles
  • Sch 39304
  • tetraconazole
  • Oxidoreductases
  • Sterol 14-Demethylase