We present investigations about the mechanism of action of a previously reported 4-anilino-2-trichloromethylquinazoline antiplasmodial hit-compound (), which did not share a common mechanism of action with established commercial antimalarials and presented a stage-specific effect on the erythrocytic cycle of at 8 < t < 16 h. The target of was searched by immobilising the molecule on a solid support a linker and performing affinity chromatography on a plasmodial lysate. Several anchoring positions of the linker (6,7 and 3′) and PEG-type linkers were assessed, to obtain a linked-hit molecule displaying antiplasmodial activity similar to that of unmodified . This allowed us to identify the PYK-1 kinase and the Rab6 GTP-ase as potential targets of .

中文翻译：

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目标钓鱼揭示 PfPYK-1 和 PfRab6 是抗疟原虫 4-苯胺基-2-三氯甲基喹唑啉命中化合物的潜在目标

我们对先前报道的 4-苯胺基-2-三氯甲基喹唑啉抗疟原虫命中化合物 () 的作用机制进行了研究，该化合物与现有的商业抗疟药没有共同的作用机制，并且对红细胞周期呈现阶段特异性作用8 < t < 16 小时。通过将分子固定在固体支持物上和连接体上并对疟原虫裂解物进行亲和层析来搜索目标。评估了接头的几个锚定位置（6,7 和 3'）和 PEG 型接头，以获得显示出与未修饰的类似的抗疟原虫活性的连接命中分子。这使我们能够确定 PYK-1 激酶和 Rab6 GTP-ase 作为 的潜在靶标。