Retinoic acid metabolism inhibition by 3-azolylmethyl-1H-indoles and 2, 3 or 5-(alpha-azolylbenzyl)-1H-indoles.
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).
Le Borgne
Marc
M
Laboratoires de Chimie Organique et de Chimie Thérapeutique, UPRES EA 1155, Faculté de Pharmacie, 1 rue Gaston Veil, F-44035 Nantes, France. marc.leborgne@sante.univ-nantes.fr
Marchand
Pascal
P
Le Baut
Guillaume
G
Ahmadi
Masoud
M
Smith
H John
HJ
Nicholls
Paul J
PJ
D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006900:Hydroxylation; D066298:In Vitro Techniques; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D007654:Ketoconazole / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D014212:Tretinoin / Q000378:metabolism*; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*
C480948:5-bromo-1-ethyl-2-((4-fluorophenyl)(1H-1,2,4-triazol-1-yl)methyl)-3-methyl-1H-indole; C480947:5-bromo-1-ethyl-3-methyl-2-((phenyl)(1H-1,2,4-triazol-1-yl)methyl)-1H-indole; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007211:Indoles; D014230:Triazoles; D014212:Tretinoin; D007654:Ketoconazole