Synthesis and evaluation of original amidoximes as antileishmanial agents
Ahlem Bouhlel1, Christophe Curti, Aurélien Dumètre
1Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, Universités d'Aix-Marseille I, II, et III-CNRS, UMR 6264, 13385 Marseille cedex 05, France.
Abstract:
An original series of amidoxime derivatives was synthesized using manganese(III) acetate, Buchwald-Hartwig and Heck reactions. Two amidoximes (39 and 52) showed interesting in vitro activities toward Leishmania donovani promastigotes, exhibiting 8.3 and 8.8 μM IC(50) values. Moreover, the cytotoxicity of these compounds was evaluated on human THP1 cells, giving access to the corresponding selectivity index. Among the 25 tested compounds, amidoximes 38 and 39 and diamidoximes 50 and 52 exhibited a better selectivity index than pentamidine used as a drug compound reference.
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