| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
Amebiasis is a common worldwide diarrheal disease, caused by infection with the protozoan parasite, Entamoeba histolytica. Metronidazole has been used against amebiasis for decades despite its side effects. Therefore novel drugs with targets and modes of action different from metronidazole are urgently needed. The cysteine biosynthetic pathway is essential for the proliferation and anti-oxidative defense of E. histolytica. This pathway, consisting of two reactions catalyzed by serine acetyltransferase and cysteine synthase (CS, O-acetylserine sulfhydrylase), does not exist in humans. I selected this pathway for a rational drug target and searched selective inhibitors against this pathway from microbial secondary metabolites. More than 18,000 microbial broths were screened and then one fungal broth was selected as a potential one. Pencolide is isolated as the cysteine biosynthetic pathway inhibitor. This compound showed both inhibitory activity against CS and antiamebic activity.
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