Synthesis and evaluation of original amidoximes as antileishmanial agents.
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.
Bouhlel
Ahlem
A
Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, Universités d'Aix-Marseille I, II, et III-CNRS, UMR 6264, 13385 Marseille cedex 05, France.
Curti
Christophe
C
Dumètre
Aurélien
A
Laget
Michèle
M
Crozet
Maxime D
MD
Azas
Nadine
N
Vanelle
Patrice
P
D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D003500:Cyclization; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects; D008345:Manganese / Q000737:chemistry; D010084:Oxidation-Reduction; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D010091:Oximes; D008345:Manganese