Sulfonylamido derivatives of 2-aminophenoxathiin-10,10-dioxide and related compounds possess antifungal action due to the possible inhibition of lanosterol-14-alpha-demethylase

J Enzyme Inhib. 1998 Jul;13(4):291-310. doi: 10.3109/14756369809021477.

Abstract

Aryl/alkyl-sulfonylamido-, arylsulfenylamido-, arylcarboxamido-, and ureido/thioureido derivatives of 2-aminophenoxathiin-10,10-dioxide were prepared by reaction with sulfonyl/sulfenyl halides, sulfonic acid anhydrides, acyl chlorides, tosyl isocyanate, aryl/allyl isocyanates or isothiocyanates. Some of these derivatives, containing free amino groups, were further derivatized by reaction with 2,4,6-trisubstituted-pyrylium salts, aryl/allyl isocyanate/isothiocyanates or tosyl isocyanate. Several of the newly synthesized compounds act as effective antifungal agents against Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole, with minimum inhibitory concentrations in the range of 0.3-0.5 microgram/mL. Their mechanism of antifungal action is hypothesized to be due to inhibition of lanosterol-14-alpha-demethylase.

MeSH terms

  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry*
  • Antifungal Agents / pharmacology*
  • Aspergillus / drug effects
  • Candida albicans / drug effects
  • Cyclic S-Oxides / chemistry*
  • Cyclic S-Oxides / pharmacology*
  • Cytochrome P-450 Enzyme Inhibitors*
  • Heterocyclic Compounds / chemical synthesis
  • Heterocyclic Compounds / chemistry*
  • Heterocyclic Compounds / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Oxidoreductases / antagonists & inhibitors*
  • Spectrophotometry, Infrared
  • Sterol 14-Demethylase
  • Structure-Activity Relationship

Substances

  • Antifungal Agents
  • Cyclic S-Oxides
  • Cytochrome P-450 Enzyme Inhibitors
  • Heterocyclic Compounds
  • Oxidoreductases
  • Sterol 14-Demethylase