Retinoic acid metabolism inhibition by 3-azolylmethyl-1H-indoles and 2, 3 or 5-(alpha-azolylbenzyl)-1H-indoles

J Enzyme Inhib Med Chem. 2003 Apr;18(2):155-8. doi: 10.1080/1475636032000069819.

Abstract

Among a library of 70 azoles, 8 indole derivatives substituted in the 2-, 3- or 5- position with an azolylmethyl or alpha-azolylbenzyl chain were evaluated for retinoic acid (RA) metabolism inhibitory activity. The most active inhibitors identified in this study were 5-bromo-1-ethyl-3-methyl-2-[(phenyl)(1H-1,2,4-triazol-1-yl)methyl]-1H-indole (3) (68.9% inhibition) and 5-bromo-1-ethyl-2-[(4-fluorophenyl) (1H-1,2,4-triazol-1-yl)methyl]-3-methyl-1H-indole (6) (60.4% inhibition). At the same concentration (100 microM) ketoconazole exerted similar inhibitory effect (70% inhibition).

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Hydroxylation
  • In Vitro Techniques
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Ketoconazole / pharmacology
  • Microsomes, Liver / enzymology
  • Microsomes, Liver / metabolism
  • Molecular Structure
  • Rats
  • Structure-Activity Relationship
  • Tretinoin / metabolism*
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • 5-bromo-1-ethyl-2-((4-fluorophenyl)(1H-1,2,4-triazol-1-yl)methyl)-3-methyl-1H-indole
  • 5-bromo-1-ethyl-3-methyl-2-((phenyl)(1H-1,2,4-triazol-1-yl)methyl)-1H-indole
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Indoles
  • Triazoles
  • Tretinoin
  • Ketoconazole