Evaluation of anti-coccidial effects of 1-[4-(4-nitrophenoxy)phenyl]propane-1-one and identification of its potential target proteins in Toxoplasma gondii.
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.
Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine, 460 Iksandae-ro, Iksan, 570-749, Jeonbuk, Republic of Korea.
Hwa-Jung
HJ
Choi
Jae-Hoon
JH
Lee
Seon-Ju
SJ
Yeo
Kusuma
K
Kaewintajuk
Kyu-Yang
KY
Yi
Suk
S
Kim
Hyun-Ok
HO
Song
Hyun
H
Park
D000818:Animals; D002645:Chickens; D003049:Coccidiostats / Q000008:administration & dosage* / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D014122:Toxoplasma / Q000187:drug effects*; D014123:Toxoplasmosis / Q000188:drug therapy* / Q000473:pathology
D003049:Coccidiostats