Previous reports have validated the glycogen synthase kinase-3 (GSK-3) as a druggable target against the human protozoan parasite Leishmania. This prompted us to search for new leishmanicidal scaffolds as inhibitors of this enzyme from our in-house library of human GSK-3β inhibitors, as well as from the Leishbox collection of leishmanicidal compounds developed by GlaxoSmithKline. As a result, new leishmanicidal inhibitors acting on Leishmania GSK-3 at micromolar concentrations were found. These inhibitors belong to six different chemical classes (thiadiazolidindione, halomethylketone, maleimide, benzoimidazole, N-phenylpyrimidine-2-amine and oxadiazole). In addition, the binding mode of the most active compounds into Leishmania GSK-3 was approached using computational tools. On the whole, we have uncovered new chemical scaffolds with an appealing prospective in the development and use of Leishmania GSK-3 inhibitors against this infectious protozoan.

中文翻译：

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旨在发现能够抑制利什曼原虫GSK-3的新型利什曼杀伤性支架。

先前的报道已经验证了糖原合酶激酶3（GSK-3）作为针对人类原生动物寄生虫利什曼原虫的可治疗靶标。这促使我们从我们的人类GSK-3β抑制剂内部库中以及葛兰素史克（GlaxoSmithKline）开发的Leishbox集合的Leishbox化合物中寻找作为该酶抑制剂的新的Leishman杀伤性支架。结果，发现了以微摩尔浓度作用于利什曼原虫GSK-3的新的利什曼杀菌剂。这些抑制剂属于六种不同的化学类别（噻二唑烷二酮，卤代甲基酮，马来酰亚胺，苯并咪唑，N-苯基嘧啶-2-胺和恶二唑）。另外，使用计算工具来研究最具活性的化合物与利什曼原虫GSK-3的结合模式。总体上，