Abstract
Coccidiosis affects many vertebrates worldwide, but treatment with known anti-coccidial drugs causes several adverse side effects. There is a critical need for the development and evaluation of new drugs. The anti-coccidial effect of 1-[4-(4-nitrophenoxy)phenyl]propane-1-one (NPPP), a synthetic compound, was studied in vitro and in vivo. Treatment with NPPP showed anti-Toxoplasma activity in vitro with a lower EC50 value than pyrimethamine. In ICR mice infected with Toxoplasma gondii, oral administration of NPPP for 4 days showed statistically significant anti-Toxoplasma activity with lower numbers of tachyzoite than those of the negative control (p < 0.01). NPPP also exhibited strong anti-Eimeria activity in Eimeria tenella-infected chickens when treated for 4 days with orally administered NPPP at a dose of 100 mg/kg. Potential target proteins of NPPP were analyzed by proteomic profiles of T. gondii tachyzoites. Two hypothetical proteins were identified as possible targets of NPPP, a putative ortholog of vacuolar ATP synthase subunit C and a class I S-adenosylmethionine-dependent methyltransferase. Our data show that the NPPP might be an anti-coccidial drug candidate for clinical application against coccidial infections. Future investigations will focus on identifying the function of proteins regulated by NPPP.
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Acknowledgments
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MEST) (No. 2010-0015187) and by the Public Welfare & Safety Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2010-0020803).
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Hwa-Jung Choi, Jae-Hoon Lee and Seon-Ju Yeo have contributed equally to this study.
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Choi, HJ., Lee, JH., Yeo, SJ. et al. Evaluation of anti-coccidial effects of 1-[4-(4-nitrophenoxy)phenyl]propane-1-one and identification of its potential target proteins in Toxoplasma gondii . Arch. Pharm. Res. 38, 752–760 (2015). https://doi.org/10.1007/s12272-014-0400-y
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DOI: https://doi.org/10.1007/s12272-014-0400-y