Sección de Síntesis, Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain.
Eur J Med Chem. 2011 Aug;46(8):3315-23. doi: 10.1016/j.ejmech.2011.04.054. Epub 2011 Apr 28.
Thirty five selenocyanate and diselenide compounds were subjected to in vitro screening against Leishmania infantum promastigotes and the most active ones were also tested in an axenic amastigote model. In order to establish the selectivity indexes (SI) the cytotoxic effect of each compound was also assayed against Jurkat and THP-1 cell lines. Thirteen derivatives exhibit better IC(50) values than miltefosine and edelfosine. Bis(4-aminophenyl)diselenide exhibits the best activity when assayed in infected macrophages and one of the lowest cytotoxic activities against the human cell lines tested, with SI values of 32 and 24 against Jurkat and THP-1 cells, respectively. This compound thus represents a new lead for further studies aimed at establishing its mechanism of action.
对 35 种硒氰化物和二硒化物化合物进行了体外筛选,以对抗利什曼原虫前鞭毛体,最有效的化合物也在无细胞内鞭毛体模型中进行了测试。为了建立选择性指数(SI),还针对 Jurkat 和 THP-1 细胞系测定了每种化合物的细胞毒性。13 种衍生物的 IC50 值优于米替福新和埃度福辛。双(4-氨基苯基)二硒化物在感染的巨噬细胞中表现出最好的活性,并且对测试的人细胞系的细胞毒性最低,对 Jurkat 和 THP-1 细胞的 SI 值分别为 32 和 24。因此,该化合物为进一步研究其作用机制提供了新的线索。