Synthesis and evaluation of monoamidoxime derivatives: Toward new antileishmanial compounds

Lucie Paloque (1, 2) , Ahlem Bouhlel (3) , Christophe Curti (3, 4) , Aurélien Dumètre (5) , Pierre Verhaeghe (2) , Nadine D Azas (5) , Patrice Vanelle (3, 4)

1 UT3 - Université Toulouse III - Paul Sabatier
2 LCC - Laboratoire de chimie de coordination
3 ICR - Institut de Chimie Radicalaire
4 APHM - Assistance Publique - Hôpitaux de Marseille
5 IP-TPT - Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques

A new series of monoamidoxime derivatives was synthesized using manganese(III) acetate by microwave irradiation. Several amidoximes (27-31, 33, 38) showed valuable in vitro activities toward Leishmania donovani promastigotes, exhibiting IC(50) values between 5.21 and 7.89 mu M. In parallel, the cytotoxicity of these compounds was evaluated on murine J774A.1 cells, revealing the corresponding selectivity index (SI). Among the 13 tested compounds, 4 monoamidoximes (27-30) exhibited an SI more than 20 times better than pentamidine. Moreover, monoamidoxime 28 (4-[5-Benzyl-3-(4-fluorophenylsulfonyl)-5-methyl-4,5-dihydrofuran-2-yl]- N'-hydroxybenzimidamide) is 40 times more selective than pentamidine, and 1.6 times more than amphotericin B, used as reference drug compounds. (C) 2011 Elsevier Masson SAS. All rights reserved.

Domaines: Chimie

Lucie Paloque, Ahlem Bouhlel, Christophe Curti, Aurélien Dumètre, Pierre Verhaeghe, et al.. Synthesis and evaluation of monoamidoxime derivatives: Toward new antileishmanial compounds. European Journal of Medicinal Chemistry, 2011, 46 (7), pp.2984--2991. ⟨10.1016/j.ejmech.2011.04.026⟩. ⟨hal-01460338⟩