title: Synthesis and evaluation of monoamidoxime derivatives: toward new antileishmanial compounds.
abstract: 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 μM. 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.
authors.affiliation: UMR-MD3-Relations Hôte-Parasites, Pharmacologie et Thérapeutique, Faculté de Pharmacie, Université d'Aix-Marseille II, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Paloque
authors.forename: Ahlem
authors.initials: A
authors.lastname: Bouhlel
authors.forename: Christophe
authors.initials: C
authors.lastname: Curti
authors.forename: Aurélien
authors.initials: A
authors.lastname: Dumètre
authors.forename: Pierre
authors.initials: P
authors.lastname: Verhaeghe
authors.forename: Nadine
authors.initials: N
authors.lastname: Azas
authors.forename: Patrice
authors.initials: P
authors.lastname: Vanelle
mesh_terms: D000085:Acetates / Q000737:chemistry; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D008018:Life Cycle Stages / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D008872:Microwaves; D009942:Organometallic Compounds / Q000737:chemistry; D010091:Oximes / Q000138:chemical synthesis* / Q000494:pharmacology; D010419:Pentamidine / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000085:Acetates; D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D010091:Oximes; C521134:manganese(III) acetate dihydrate; D010419:Pentamidine; D000666:Amphotericin B