6-trifluoromethyl-2-thiouracil possesses anti-Toxoplasma gondii effect in vitro and in vivo with low hepatotoxicity.
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.
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. Electronic address: rerived@kwu.ac.kr.
Hwa-Jung
HJ
Choi
Department of Pediatrics, Wonkwang University School of Medicine, 460 Iksandae-ro, Iksan, Jeonbuk 570-749, Republic of Korea.
Seung-Taek
ST
Yu
Korea Chemical Bank, Korea Research Institute of Chemical Technology, 141 Gagjeong-ro, Yuseong, Daejeon 305-600, Republic of Korea.
Kee-In
KI
Lee
Korea Chemical Bank, Korea Research Institute of Chemical Technology, 141 Gagjeong-ro, Yuseong, Daejeon 305-600, Republic of Korea.
Joong-Kwon
JK
Choi
Department of Pharmacy, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 570-749, Republic of Korea.
Bo-Yoon
BY
Chang
Department of Pharmacy, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 570-749, Republic of Korea.
Sung-Yeon
SY
Kim
Division of Mathematics and Informational Statistics, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 570-749, Republic of Korea.
Mi-Hwa
MH
Ko
Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine, 460 Iksandae-ro, Iksan, Jeonbuk 570-749, Republic of Korea. Electronic address: hosong@wonkwang.ac.kr.
Hyun-Ok
HO
Song
Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine, 460 Iksandae-ro, Iksan, Jeonbuk 570-749, Republic of Korea. Electronic address: hyunpk@wonkwang.ac.kr.
Hyun
H
Park
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D003049:Coccidiostats / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013889:Thiouracil / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014122:Toxoplasma / Q000187:drug effects*; D014123:Toxoplasmosis / Q000188:drug therapy*
C000591391:6-trifluoromethyl-2-thiouracil; D003049:Coccidiostats; D013889:Thiouracil; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione
Anti-Toxoplasma gondii activity; KH-0562; Toxoplasmosis