Synthesis and evaluation of monoamidoxime derivatives: Toward new antileishmanial compounds

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 IC50 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.

Graphical abstractAn original series of monoamidoxime derivatives was synthesized using manganese(III) acetate. Compounds were tested for their in vitro activities toward Leishmania donovani, and for their cytotoxicity on J774A.1 cells.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis of original series of monoamidoxime derivatives. ► Synthesis via manganese(III) acetate methodology by microwave irradiation. ► In vitro activities toward Leishmania donovani promastigotes. ► moderate cytotoxicity on murine J774A.1 cells.