Search for natural products which inhibit Entamoeba histolytica cysteine synthase
| Project/Area Number |
26460129
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Natural medicines
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| Research Institution | Kitasato University |
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Principal Investigator |
Mori Mihoko 北里大学, 感染制御科学府, 助教 (20425648)
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| Research Collaborator |
NOZAKI Tomoyoshi 国立感染症研究所, 部長
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| 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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| Keywords | 赤痢アメーバ / Entamoeba histolytica / システイン生合成経路 / cysteine synthase / 微生物代謝産物 / スクリーニング / システイン合成 / 微生物二次代謝産物 / システイン生合成 / xanthomegnin / pencolide / ovalicin |
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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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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Identification of natural inhibitors of Entamoeba histolytica cysteine synthase from microbial secondary metabolites2015
Author(s)
Mori, M., Jeelani, G., Masada, Y., Sakai, K., Tsukui, K., Waluyo, D., Watanabe, Y., Nonaka, K., Matsumoto, A., Omura, S., Nozaki, T., Shiomi, K.
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Journal Title
Frontiers in Microbiology
Volume: 6
Pages: 962-962
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Identification of natural inhibitors of Entamoeba histolytica cysteine synthase from microbial secondary metabolites2015
Author(s)
Mori, M, Jeelani, G., Masuda, Y., Sakai, K., Tsukui, K., Waluyo, D., Watanabe, Y., Nonaka, K., Matsumoto, A., Omura, S., Nozaki, T., Shiomi, K.
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Journal Title
Frontiers in Microbiology
Volume: 印刷中
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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