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Screening of Plasmodium falciparum enoyl-Acyl carrier protein reductase (PfFabI) inhibitors from microbial metabolites for prophylaxis and blocking transmission of malaria

Research Project

Project/Area Number 26460128
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Natural medicines
Research InstitutionKitasato University

Principal Investigator

Aki Ishiyama  北里大学, 感染制御科学府, 特任助教 (70300746)

Co-Investigator(Renkei-kenkyūsha) IWATSUKI MASATO  北里大学, 北里生命化学研究所感染制御科学府, 准教授 (70353464)
MATSUMOTO ATSUKO  北里大学, 北里生命化学研究所感染制御科学府, 准教授 (20300759)
NONAKA KENICHI  北里大学, 北里生命化学研究所感染制御科学府, 助教 (60421369)
HIROSE TOMOYASU  北里大学, 北里生命化学研究所感染制御科学府, 准教授 (00370156)
IKADAI HIROMI  北里大学, 獣医学部, 准教授 (80327460)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordspfFabI / マラリア原虫 / マラリア感染予防 / TypeII脂肪酸合成酵素 / 微生物代謝産物
Outline of Final Research Achievements

To crate the safer antimalarial drugs for the prophylaxis and transmission blocking, we have focused on the type II fatty acid synthetic system of Plasmodium falciparum. The enoyl-acyl carrier protein reductase (pfFabI) is a key enzyme for the parasite division and proliferation in liver stage parasite before the onset of malaria symptoms such as a fever, anemia and sometime death for its severe. We have carried out the screening to discover pfFabI inhibitors from microbial metabolites, total 14 compounds from microbial metabolites were identified showing pfFabI inhibitory activity with new knowledge. Among them complestatin and chloropeptin I isolated from Streptomyces sp. K12-0828 showed the most potent pfFabI inhibitory activity with the IC50 of 4.8 and 5.8 microM, respectively. Additionally, complestatin and chloropeptin I showed as effective as pfFabI inhitory activity against liver stage malaria parasites that was also new knowledge.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (2 results)

All 2016 2015

All Presentation (2 results)

  • [Presentation] 「微生物代謝産物からのマラリア原虫脂肪酸 合成酵素 (pfFabI)阻害活性物質の探索研究」2016

    • Author(s)
      石山亜紀、岩月正人、穗苅玲、野中健一、松本厚子、高橋洋子、乙黒和彦、大村智
    • Organizer
      第57 会日本熱帯医学会大会日本熱帯医学
    • Place of Presentation
      一橋大学 一橋講堂(東京都、千代田区)
    • Year and Date
      2016-11-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] 微生物代謝産物からのマラリア脂肪酸合成酵素pfFabI阻害物質の探索2015

    • Author(s)
      浮山颯、岩月正人、野中健一、松本厚子、石山亜紀、穗苅玲、乙黒和彦、大村智、塩見和郎
    • Organizer
      日本農芸化学会 2015年度大会
    • Place of Presentation
      岡山県岡山市
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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