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Studies On The Bioactive Secondary Metabolites Of Five Strains Of Microorganism

Posted on:2013-03-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:R DingFull Text:PDF
GTID:1224330482962692Subject:Natural medicinal chemistry
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As an important source of leading compounds, natural products play an important role in research and discovery (R & D) of new drugs. Thereamong, much attention has been paid to the secondary metabolites of microorganism due to their novel structures, broad spectrum of bioactivities and abundant resources. But after massive isolation and screening, it has been more and more difficult to find new bioactive compounds from terrestial microorganism. So scientists have focused their attention on the microorganism derived from special ecological environment recently.As mentioned above, my research work was focused on the bioactive secondary metabolites of microorganisms from special ecological environment. In this work, from two strains of Endolichenic fungi of Sarcosomataceae, two strains of Streptomyces from mangrove soil and Streptomyces venezuelae ATCC 15439,43 compounds were isolated by silica gel, sephadex LH-20, ODS column chromatography and reversed-phase high performance liquid chromatography (RP HPLC). All their planar structures were elucidated primarily by mass spectrometry (MS) and nuclear magnetic resonance (NMR). The stereochemistry of part of compounds was determined by CD calculation and CD exciton chirality methods. Among these compounds, there were 19 new compounds, including 2 previously undescribed skeletons and 6 new spirobisnaphthalene.In addition, the biosysthetic pathways of spirobisnaphthalenes (1-6) and sarcosolactones (10, 11) were proposed. Furthermore, some compounds were evaluated for their inhibitory effects against the proliferation of human tumor cell lines (MTT) and human T cell proliferation mediated by PMA/ionomycin. The results revealed that compounds 1 and 2 exhibited significant inhibitory effects on the proliferation of human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480), even better than that of positive control Cisplatin; compound 3 have an moderate effect on the proliferation of human tumor cell lines. Compounds 35,36,38,41 and 43 showed significant inhibitory effects on human T cell proliferation mediated by PMA/ionomycin at a concentration of 100μM. Among them, compound 41 showed the most potential activities with an IC50 value of 9.89 μM. The researches might provide chemical bases for the discovery of new anti-cancer and anti-inflammatory drugs.
Keywords/Search Tags:Endolichenic fungi, mangrove, Sarcosomataceae, Streptomyces, secondary metabolites, bioactivity in vitro
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