title: In vitro inhibition of Toxoplasma gondii by the anti-malarial candidate, 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol.
abstract: An anti-malarial candidate, 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251), was studied to characterize its potential as a novel anti-Toxoplasma gondii drug. In the present study, IC50 and LC50 of N-251 on host cells and T. gondii were compared to those of artemisinin and sulfadiazine. The IC50 on Huh-7 cells was 10.19μg/ml, 67.69μg/ml and 310.17μg/ml for N-251, artemisinin, and sulfadiazine, respectively. The LC50 for anti-T. gondii effect was shown to be 1.11μg/ml, 5.79μg/ml, and 5.45μg/ml for N-251, artemisinin and sulfadiazine, respectively. N-251 concentration causing complete parasiticidal effect with minimal cytotoxicity on host cells was determined to be 5μg/ml. Additionally, the anti-T. gondii effect of N-251 was confirmed by ultrastructural changes, loss of organelles, degenerated morphology and the increase of amylopectin as detected by transmission electron microscope (TEM). Accordingly, the present study suggests that the anti-malarial synthetic endoperoxide, N-251, is an emerging drug candidate more effective than artemisinin and sulfadiazine.
authors.affiliation: Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul 110-799, Republic of Korea.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Xin
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan.
authors.forename: Hye-Sook
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul 110-799, Republic of Korea.
authors.forename: Hak-Jae
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul 110-799, Republic of Korea.
authors.forename: You-Won
authors.initials: YW
authors.lastname: Lee
authors.affiliation: Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul 110-799, Republic of Korea.
authors.forename: Kyoung-Ho
authors.initials: KH
authors.lastname: Pyo
authors.affiliation: Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul 110-799, Republic of Korea; Seoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea. Electronic address: ehshin@snu.ac.kr.
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Shin
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D021261:Parasitic Sensitivity Tests; D013141:Spiro Compounds / Q000494:pharmacology*; D013411:Sulfadiazine / Q000494:pharmacology; D045568:Tetraoxanes / Q000494:pharmacology*; D014122:Toxoplasma / Q000187:drug effects*
chemical_list: C571809:6-(1,2,6,7-tetraoxaspiro(7.11)nonadec-4-yl)hexan-1-ol; D000962:Antimalarials; D037621:Artemisinins; D013141:Spiro Compounds; D045568:Tetraoxanes; D013411:Sulfadiazine; C031327:artemisinin
keywords: Anti-malarial candidate; Anti-protozoal activity; N-251; Synthetic endoperoxide; Toxoplasma gondii; Transmission electron microscopy