Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 143-8501, Japan.
Bioorg Med Chem. 2010 Nov 15;18(22):7804-8. doi: 10.1016/j.bmc.2010.09.054. Epub 2010 Sep 26.
SSJ-127, a novel antimalarial rhodacyanine derivative, has shown potent antimalarial activity against chloroquine-resistant Plasmodium strains in vitro and subcutaneous administration of SSJ-127 results in a complete cure of a mouse malaria model. SSJ-127 was detected by fluorescence microscopy in the mouse malaria parasites Plasmodium berghei after exposure of infected red blood cells to the compound in vitro and in vivo. Selective accumulation of SSJ-127 in an organelle is observed in all blood stages of live malaria parasites. The organelle is clearly different from the mitochondrion and the nucleus in terms of morphology. The shape of the organelle changed during the asexual blood stages of the parasite. There was always a close association between the organelle and the mitochondrion. These results raised the possibility that SSJ-127 accumulates in an apicoplast of the malaria parasite and affects protozoan parasite-specific pathways.
SSJ-127 是一种新型抗疟吖啶衍生物，在体外对氯喹耐药的疟原虫表现出强大的抗疟活性，皮下给予 SSJ-127 可完全治愈小鼠疟疾模型。在体外和体内实验中，用荧光显微镜观察到 SSJ-127 在感染的红细胞中暴露于该化合物后，在小鼠疟原虫寄生虫疟原虫伯氏疟原虫中被检测到。在所有活体疟原虫的血阶段都观察到 SSJ-127 在细胞器中的选择性积累。该细胞器在形态上与线粒体和细胞核明显不同。在寄生虫的无性血阶段，细胞器的形状发生了变化。细胞器和线粒体之间始终存在密切的联系。这些结果提出了 SSJ-127 可能在疟原虫的顶质体中积累并影响原生动物寄生虫特异性途径的可能性。
