Inhibition of sterol 14 α-demethylation of Candida albicans with NND-502, a novel optically active imidazole antimycotic agent

Yoshimi Niwano, H. Koga, H. Kodama, K. Kanai, T. Miyazaki, H. Yamaguchi

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

To investigate the mode of action of the newly synthesized optically active imidazole compound, NND-502, (-)-(E)-[4-(2,4-dichlorophenyl)-1,3-dithiolan-2-ylidene]-1 -imidazolylacetonitrile, its effect on ergosterol biosynthesis in cell-free extracts of Candida albicans was examined and compared with that of the (S)-enantiomer of NND-502 in addition to lanoconazole and bifonazole, both of which are clinically used for the treatment of dermatomycoses. NND-502 was found to interfere with ergosterol biosynthesis by inhibition of sterol 14α-demethylase, while no interference due to the (S)-enantiomer of NND-502 was found, indicating that the stereochemical orientation of the 2,4-dichlorophenyl group plays an important role in the interaction with the enzyme. In terms of drug concentration exerting 50% inhibition of ergosterol biosynthesis, NND-502 was 2.5 and 28 times more effective than that of lanoconazole and bifonazole, respectively.

Original languageEnglish
Pages (from-to)351-355
Number of pages5
JournalMedical Mycology
Volume37
Issue number5
DOIs
Publication statusPublished - 1999 Oct

Keywords

  • Candida albicans
  • Ergosterol synthesis
  • Imidazole antimycotic
  • NND-502

ASJC Scopus subject areas

  • Infectious Diseases

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