Synthesis and antileishmanial activity of 3-(alpha-azolylbenzyl)indoles.
The goal of the present study was to evaluate several azolyl-substituted indoles as new antileishmanial agents. Ten 3-(alpha-azolylbenzyl)indoles have been synthesized using Friedel-Crafts acylation as a key-step. All the target compounds were found to display high levels of activity when tested against Leishmania mexicana promastigotes in vitro. The most active compounds, showing an IC50 < 1 microM, were 5-bromo-1-ethyl-3-[(2,4-dichlorophenyl)(1H-imidazol-1-yl)methyl]-1H-indole 15 and its triazole analogue 17. Four representative compounds 15, 17, 22 and, 23 were also tested against intracellular amastigotes of L. mexicana using ketoconazole and meglumine antimoniate as reference compounds, the results of which are discussed.
Marchand
Pascal
P
Laboratoire de Chimie Organique, UPRES EA 1155, Faculté de Pharmacie, 1 rue Gaston Veil, F-44035 Nantes, France.
Le Borgne
Marc
M
Na
Young Min
YM
Pagniez
Fabrice
F
Abdala
Hiam
H
Le Baut
Guillaume
G
Le Pape
Patrice
P
D000215:Acylation; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007894:Leishmania mexicana / Q000187:drug effects; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D007211:Indoles