Schistosomicidal and antifecundity effects of oral treatment of synthetic endoperoxide N-89

Toshie Taniguchi, Takashi Kumagai, Rieko Shimogawara, Shizuko Ichinose, Akiko Hiramoto, Akira Sato, Masayuki Morita, Masatomo Nojima, Hye Sook Kim, Yusuke Wataya, Nobuo Ohta

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

1,2,6,7-Tetraoxaspiro[7.11]nonadecane (N-89) is a chemically synthesized compound with good efficacy against malaria parasites. We observed strong anti-schistosomal activities of N-89 both in vitro and in vivo. In a murine model with experimental infection of Schistosoma mansoni, orally administered N-89 at the dose of 300. mg/kg resulted in a significant reduction in worm burden (63%) when mice were treated at 2-weeks postinfection. Strong larvicidal effects of N-89 were confirmed in vitro; schistosomula of S. mansoni were killed by N-89 at an EC50 of 16. nM. In contrast, no significant reduction in worm burden was observed when N-89 was administered at 5. weeks postinfection in vivo. However, egg production was markedly suppressed by N-89 treatment at that time point. On microscopic observation, the intestine of N-89-treated female worms seemed to be empty compared with the control group, and the mean body length was significantly shorter than that of controls. Nutritional impairment in the parasite due to N-89 treatment was possible, and therefore quantification of hemozoin was compared between parasites with or without N-89 treatment. We found that the hemozoin content was significantly reduced in N-89 treated parasites compared with controls (P<0.001). The surface of adult worms was observed by scanning and transmission electron microscopy, but there were no apparent changes. Taken together, these observations suggested that N-89 has strong antischistosomal effects, probably through a unique mode of drug efficacy. As N-89 is less toxic to mammalian host animals, it is a possible drug candidate against schistosomiasis.

Original languageEnglish
Pages (from-to)231-236
Number of pages6
JournalParasitology International
Volume60
Issue number3
DOIs
Publication statusPublished - Sep 2011

Keywords

  • Fecundity
  • Hemozoin
  • N-89
  • Schistosoma mansoni
  • Worm burden

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

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