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

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460128
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Natural medicines
• Research Institution: Kitasato 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
• Keywords: pfFabI / 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.

Free Research Field

寄生虫学　生化学