Paloque Lucie, Bouhlel Ahlem, Curti Christophe, Dumètre Aurélien, Verhaeghe Pierre, Azas Nadine, Vanelle Patrice
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.
Eur J Med Chem. 2011 Jul;46(7):2984-91. doi: 10.1016/j.ejmech.2011.04.026. Epub 2011 Apr 15.
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.
通过微波辐射，利用醋酸锰合成了一系列新的单脒基肟衍生物。几种脒基肟（27 - 31、33、38）对杜氏利什曼原虫前鞭毛体显示出有价值的体外活性，IC(50)值在5.21至7.89 μM之间。同时，评估了这些化合物对小鼠J774A.1细胞的细胞毒性，得出相应的选择性指数（SI）。在13种测试化合物中，4种单脒基肟（27 - 30）的SI比喷他脒高出20倍以上。此外，单脒基肟28（4 - [5 - 苄基 - 3 - (4 - 氟苯基磺酰基) - 5 - 甲基 - 4,5 - 二氢呋喃 - 2 - 基] - N' - 羟基苯甲酰胺）的选择性比喷他脒高40倍，比用作参考药物化合物的两性霉素B高1.6倍。
