title: Stage specific activity of synthetic antimalarial endoperoxides, N-89 and N-251, against Plasmodium falciparum.
abstract: We have reported that two endoperoxides, N-89 and N-251, synthesized in 2001, possess potent antimalarial activities. Aiming at their eventual use for curing malaria in humans, we have been investigating various aspects of their antimalarial actions. Here we show that N-89 and N-251 inhibit the growth of Plasmodium falciparum within human erythrocytes in vitro at its lifecycle stage 'trophozoite' specifically. It is known that artemisinin compounds, which are currently used for curing malaria, have other stage-specificities. Therefore, it is likely that the antimalarial mechanism of N-89 and N-251 differs from those of artemisinin compounds. As malaria parasites resistant to artemisinin-based combination therapy are currently emerging in some tropical regions, N-89 and N-251 are candidates for overcoming these new problems.
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan; Division of Malaria Research, Proteo-Science Center, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime 790-8577, Japan. Electronic address: morita.masayuki.ls@ehime-u.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Morita
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan. Electronic address: takapinok0128@gmail.com.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan. Electronic address: sanao14@yahoo.co.jp.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sanai
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan; Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: akirasat@rs.tus.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan. Electronic address: akihira1076@gmail.com.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hiramoto
authors.affiliation: Faculty of Engineering, Osaka Institute of Technology, 5-16-1 Ohmiya, Asahiku, Osaka 535-8585, Japan. Electronic address: masuyama@chem.oit.ac.jp.
authors.forename: Araki
authors.initials: A
authors.lastname: Masuyama
authors.affiliation: Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address: m-nojima@mx5.canvas.ne.jp.
authors.forename: Masatomo
authors.initials: M
authors.lastname: Nojima
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan. Electronic address: wataya@cc.okayama-u.ac.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Wataya
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan. Electronic address: hskim@cc.okayama-u.ac.jp.
authors.forename: Hye-Sook
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D004912:Erythrocytes / Q000469:parasitology; D006574:Heterocyclic Compounds, 2-Ring / Q000494:pharmacology*; D006801:Humans; D008288:Malaria / Q000469:parasitology; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D013141:Spiro Compounds / Q000494:pharmacology*; D045568:Tetraoxanes / Q000494:pharmacology*; D053058:Trophozoites / Q000187:drug effects / Q000648:ultrastructure
chemical_list: C430901:1,2,6,7-tetraoxaspiro(7.11)nonadecane; C571809:6-(1,2,6,7-tetraoxaspiro(7.11)nonadec-4-yl)hexan-1-ol; D000962:Antimalarials; D037621:Artemisinins; D006574:Heterocyclic Compounds, 2-Ring; D013141:Spiro Compounds; D045568:Tetraoxanes; C031327:artemisinin
keywords: Antimalarial candidates; N-251; N-89; Stage-specificity; Synthetic endoperoxides