Synthesis and evaluation of original amidoximes as antileishmanial agents.

Authors :: Bouhlel A
Curti C
Dumètre A
Laget M
Crozet MD
Azas N
Vanelle P
Source :: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2010 Oct 15; Vol. 18 (20), pp. 7310-20. Date of Electronic Publication: 2010 Jul 11.
Publication Year :: 2010
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.<br /> (Copyright © 2010 Elsevier Ltd. All rights reserved.)