| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
In our screening program on immunomodulatory components from fungi, crude extracts of several fungi among ca. 150 species of fungi showed significantly suppressive activity against blastogenesis of mouse splenic lymphocytes. Chromatographic fractionations of these active extracts guided by immunosuppressive activity afforded several immunosuppressive constituents, namely, nine new 2-pyrones, multiforisins A(1)-I(9), from Gelasinospora multiforis, a new macrocyclic sesterterpene kobiin (10), and three new 2-furanones, kobifuranones A(11)- C(13), from Gelasinospora kobi, a 2-pyrone, macrophin(14) (a metaboilte of Macrophoma commelinae), two macrocyclic lactones, colletodiol(15) (a metabolite of Colletotricum capsici and Chaetomium funicola) and its new stereoisomer 10-epi-colletodiol(16) from Diplogelasino- spora grovesii, 7-9 and a hexaketide, sordarial(17) (a metabolite of Sordaria macrospora), from Gelasinospora heterospora, and 1, 7-9, and 17 from Gelasinospora longispora. To our knowledge, this is the first time that the three known components 14, 15, and 17 have been isolated as immunosuppressive constituents from natural sources, and the absolute. configuration of the side chain in 17, which had been not yet decided, has been completely determined this time. Structure-activity relationship of immunosuppressive 2-pyrones including twelve compounds, namely, 1-9, two their derivatives and 14, has been elucidated. Comparison of the mode of action of one of the multiforisins, 7, with that of FK506 indicated that the immunosuppressive activity of 7 was not due to inhibition of interleukin 2 production. Other some immunosuppressive components have been also isolated from Gelasinospora santi-florli, Microascus tardifaciens, and other several Ascomycetes, and their structures were also elucidated.
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