Choi Hwa-Jung, Yu Seung-Taek, Lee Kee-In, Choi Joong-Kwon, Chang Bo-Yoon, Kim Sung-Yeon, Ko Mi-Hwa, Song Hyun-Ok, Park Hyun
Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine, 460 Iksandae-ro, Iksan, Jeonbuk 570-749, Republic of Korea; Department of Beauty Science, Kwangju Women's University, 165 Sanjeong-dong, Gwangsan-gu, Gwangju 506-713, Republic of Korea.
Department of Pediatrics, Wonkwang University School of Medicine, 460 Iksandae-ro, Iksan, Jeonbuk 570-749, Republic of Korea.
Exp Parasitol. 2014 Aug;143:24-9. doi: 10.1016/j.exppara.2014.05.002. Epub 2014 May 14.
Since pyrimethamine, the general therapeutic drug for toxoplasmosis, presents several adverse side effects, the need to develop and evaluate new drugs for the condition is critical. In this study, anti-Toxoplasma gondii activities of 3-[{2-((E)-furan-2-ylmethylene)hydrazinyl}methylene]-1,3-dihydroindol-2-one (ATT-5126) and 6-trifluoromethyl-2-thiouracil (KH-0562) were evaluated in vitro using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and in vivo by measuring amount of the tachyzoites in mice ascites. Biochemical parameters such as lipid peroxidation (LPO), glutathione (GSH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were also evaluated in livers of mice at 4 days post-infection. As a result, the ATT-5126 and KH-0562 showed anti-T. gondii activity in vitro. Treatment of ATT-5126 or KH-0562 decreased the amount of tachyzoites in T. gondii infected ICR mice. The relative weight of liver and spleen increased by T. gondii infection were decreased by treatment of ATT-5126 or KH-0562. The levels of LPO, ALT and AST, which are biochemical parameters involved in liver injury, were also significantly recovered by treatment of ATT-5126 or KH-0562 (p<0.05). In particular, the recovered levels by KH-0562 were similar to those of pyrimethamine-treated group (p<0.05). However, the level of GSH, which is an antioxidant indicator, showed insignificant statistics. The results suggest that KH-0562 show anti-T. gondii activities in vitro and in vivo with low hepatotoxicity. Therefore, KH-0562 may be a useful candidate for treating T. gondii infection.
由于治疗弓形虫病的常用药物乙胺嘧啶存在多种副作用，因此开发和评估针对该病症的新药至关重要。在本研究中，使用3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基苯基)-2-(4-磺基苯基)-2H-四氮唑（MTS）测定法在体外评估了3-[{2-((E)-呋喃-2-基亚甲基)肼基}亚甲基]-1,3-二氢吲哚-2-酮（ATT-5126）和6-三氟甲基-2-硫脲嘧啶（KH-0562）对刚地弓形虫的活性，并通过测量小鼠腹水中速殖子的数量在体内进行了评估。还在感染后4天对小鼠肝脏中的脂质过氧化（LPO）、谷胱甘肽（GSH）、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）等生化参数进行了评估。结果显示，ATT-5126和KH-0562在体外具有抗刚地弓形虫活性。用ATT-5126或KH-0562治疗可减少刚地弓形虫感染的ICR小鼠体内速殖子的数量。刚地弓形虫感染导致增加的肝脏和脾脏相对重量通过ATT-5126或KH-0562治疗而降低。参与肝损伤的生化参数LPO、ALT和AST的水平也通过ATT-5126或KH-0562治疗而显著恢复（p<0.05）。特别是，KH-0562恢复后的水平与乙胺嘧啶治疗组相似（p<0.05）。然而，作为抗氧化指标的GSH水平在统计学上无显著差异。结果表明，KH-0562在体外和体内均显示出抗刚地弓形虫活性且肝毒性较低。因此，KH-0562可能是治疗刚地弓形虫感染有用的候选药物。
