Stage specific activity of synthetic antimalarial endoperoxides, N-89 and N-251, against Plasmodium falciparum. Issue 1 (February 2015)

• Record Type: Journal Article
• Authors: Morita, Masayuki; Koyama, Takahiko; Sanai, Hitomi; Sato, Akira; Hiramoto, Akiko; Masuyama, Araki; Nojima, Masatomo; Wataya, Yusuke; Kim, Hye-Sook
• Is Part Of: Parasitology international. Volume 64:Issue 1(2015:Feb.)
• Page Start: 113
• Page End: 117
• Publication Date: 2015-02
• Subjects: Antimalarial candidates -- Synthetic endoperoxides -- N-89 -- N-251 -- Stage-specificity; Parasitology -- Periodicals; Parasites -- Periodicals; Parasitic Diseases -- Periodicals; Parasitology -- Periodicals; Parasitologie -- Périodiques; 571.99905
• DOI: 10.1016/j.parint.2014.10.007
• Languages: English
• ISSNs: 1383-5769

Abstract

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. Graphical abstract: Highlights: N-89 and N-251 act specifically on the trophozoite stage of malaria parasites. These antimalarials inhibit trophozoite parasite development. This stage-specificity is different from that of artemisinin drugs.