Hao Pan, Alaraj Intisar Q M, Dulayymi Juma'a R Al, Baird Mark S, Liu Jing, Liu Qun
National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
School of Chemistry, Bangor University, Bangor, UK.
Korean J Parasitol. 2016 Apr;54(2):139-45. doi: 10.3347/kjp.2016.54.2.139. Epub 2016 Apr 30.
Toxoplasmosis is a serious disease caused by Toxoplasma gondii, one of the most widespread parasites in the world. Lipid metabolism is important in the intracellular stage of T. gondii. Stearoyl-CoA desaturase (SCD), a key enzyme for the synthesis of unsaturated fatty acid is predicted to exist in T. gondii. Sterculic acid has been shown to specifically inhibit SCD activity. Here, we examined whether sterculic acid and its methyl ester analogues exhibit anti-T. gondii effects in vitro. T. gondii-infected Vero cells were disintegrated at 36 hr because of the propagation and egress of intracellular tachyzoites. All test compounds inhibited tachyzoite propagation and egress, reducing the number of ruptured Vero cells by the parasites. Sterculic acid and the methyl esters also inhibited replication of intracellular tachyzoites in HFF cells. Among the test compounds, sterculic acid showed the most potent activity against T. gondii, with an EC50 value of 36.2 μM, compared with EC50 values of 248-428 μM for the methyl esters. Our study demonstrated that sterculic acid and its analogues are effective in inhibition of T. gondii growth in vitro, suggesting that these compounds or analogues targeting SCD could be effective agents for the treatment of toxoplasmosis.
弓形虫病是由刚地弓形虫引起的一种严重疾病，刚地弓形虫是世界上分布最广的寄生虫之一。脂质代谢在刚地弓形虫的细胞内阶段很重要。硬脂酰辅酶A去饱和酶（SCD）是不饱和脂肪酸合成的关键酶，预计存在于刚地弓形虫中。已证明苹婆酸可特异性抑制SCD活性。在此，我们研究了苹婆酸及其甲酯类似物在体外是否具有抗刚地弓形虫的作用。由于细胞内速殖子的增殖和逸出，感染刚地弓形虫的Vero细胞在36小时时解体。所有测试化合物均抑制速殖子的增殖和逸出，减少了被寄生虫破坏的Vero细胞数量。苹婆酸及其甲酯还抑制了人包皮成纤维细胞（HFF）中细胞内速殖子的复制。在测试化合物中，苹婆酸对刚地弓形虫表现出最有效的活性，半数有效浓度（EC50）值为36.2μM，而甲酯的EC50值为248 - 428μM。我们的研究表明，苹婆酸及其类似物在体外可有效抑制刚地弓形虫的生长，这表明这些靶向SCD的化合物或类似物可能是治疗弓形虫病的有效药物。
