Parasites, Hosts and Diseases

  • 제61권1호
  • /
  • Pages.33-41
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  • 2023
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  • 2982-5164(pISSN)
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  • 1738-0006(eISSN)
대한기생충학·열대의학회 (The Korea Society for Parasitology and Tropical Medicine)
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Antimalarial effect of synthetic endoperoxide on synchronized Plasmodium chabaudi infected mice

  • Nagwa S. M. Aly (Division of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University) ;
  • Hiroaki Matsumori (Division of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University) ;
  • Thi Quyen Dinh (Division of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University) ;
  • Akira Sato (Division of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University) ;
  • Shin-Ichi Miyoshi (Department of Sanitary Microbiology, Faculty of Pharmaceutical Sciences, Okayama University) ;
  • Kyung-Soo Chang (Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan) ;
  • Hak Sun Yu (Department of Parasitology and Tropical Medicine, School of Medicine, Pusan National University) ;
  • Fumie Kobayashi (Department of Environmental Science, School of Life Environmental Science, Azabu University) ;
  • Hye-Sook Kim (Division of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University)
  • 투고 : 2022.09.10
  • 심사 : 2022.12.12
  • 발행 : 2023.02.28
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초록

The discovery of new antimalarial drugs can be developed using asynchronized Plasmodium berghei malaria parasites in vivo in mice. Studies on a particular stage are also required to assess the effectiveness and mode of action of drugs. In this report, we used endoperoxide 6-(1,2,6,7-tetraoxaspiro [7.11] nonadec-4-yl) hexan-1-ol (N-251) as a model antimalarial compound on P. chabaudi parasites. We examined the antimalarial effect of N-251 against ring-stage- and trophozoite-stage-rich P. chabaudi parasites and asynchronized P. berghei parasites using the 4-day suppressive test. The ED50 values were 27, 22, and 22 mg/kg, respectively, and the antimalarial activity of N-251 was verified in both rodent malaria parasites. To assess the stage-specific effect of N-251 in vivo, we evaluated the change of parasitemia and distribution of parasite stages using ring-stage- and trophozoite-stage-rich P. chabaudi parasites with one-day drug administration for one life cycle. We discovered that the parasitemias decreased after 13 and 9 hours post-treatment in the ring-stage- and trophozoite-stage-rich groups, respectively. Additionally, in the ring-stage-rich N-251 treated group, the ring-stage parasites hindered trophozoite parasite development. For the trophozoite-stage-rich N-251 treated group, the distribution of the trophozoite stage was maintained without a change in parasitemia until 9 hours. Because of these findings, it can be concluded that N-251 suppressed the trophozoite stage but not the ring stage. We report for the first time that N-251 specifically suppresses the trophozoite stage using P. chabaudi in mice. The results show that P. chabaudi is a reliable model for the characterization of stage-specific antimalarial effects.

키워드

과제정보

This study was partially supported by a grant from the Program of the Japan Initiative for Global Research Network on Infectious Diseases (J-GRID, JP22wm0125004) from the Ministry of Education, Culture, Sports, Science, and Technology in Japan (MEXT), and the Japan Agency for Medical Research and Development (AMED). We thank Taiki Osato (Okayama University) for the partial experiments and discussion.

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