Yang Zhaoshou, Ahn Hye-Jin, Nam Ho-Woo
Department of Parasitology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
Korean J Parasitol. 2014 Aug;52(4):439-41. doi: 10.3347/kjp.2014.52.4.439. Epub 2014 Aug 29.
Toxoplasma gondii is the causative agent of toxoplasmosis with symptoms of congenital neurological and ocular diseases and acquired lymphadenitis, retinochoroiditis, and meningoencephalitis. Small molecules which block the activity of protein kinases were tested in in vitro culture of T. gondii to find new therapeutic drugs of safer and more effective than the combined administration of pyrimethamine and sulfadoxine that sometimes provoke lethal Stevens-Johnson syndrome. Among them, Gefitinib and Crizotinib inhibited intracellular growth of T. gondii in HeLa cells by counting the number of T. gondii per parasitophorous vacuolar membrane whereas Sunitinib did not. Gefitinib inhibited the growth of T. gondii in a dose-dependent manner over 5 µM up to the tolerable concentration of HeLa cells and halted the division of the parasite immediately from the time point of treatment. Gefitinib inhibition suggests that tyrosine kinases of EGFR family or other homologous kinases of the parasite itself may be the target to cause the block of T. gondii growth.
弓形虫是弓形体病的病原体,其症状包括先天性神经和眼部疾病以及获得性淋巴结炎、视网膜脉络膜炎和脑膜脑炎。在弓形虫的体外培养中测试了阻断蛋白激酶活性的小分子,以寻找比联合使用乙胺嘧啶和磺胺多辛更安全、更有效的新治疗药物,联合使用乙胺嘧啶和磺胺多辛有时会引发致命的史蒂文斯-约翰逊综合征。其中,吉非替尼和克唑替尼通过计算每个寄生泡膜内弓形虫的数量来抑制HeLa细胞中弓形虫的细胞内生长,而舒尼替尼则没有。吉非替尼在5μM以上以剂量依赖性方式抑制弓形虫在HeLa细胞中的生长,直至HeLa细胞的耐受浓度,并从治疗时间点立即停止寄生虫的分裂。吉非替尼的抑制作用表明,EGFR家族的酪氨酸激酶或寄生虫自身的其他同源激酶可能是导致弓形虫生长受阻的靶点。