Metabolites From Two Mangrove Endophytic Fungi And Their Antimicrobial And Antitumor Activities

With the development of molecular biology, the research for new antitumor and anti-fungal compounds has deepened into the mechanism of cancer and fungal disease. On the other side, people begin to search more active leading compounds from new environments beyond terrestrial ones. The marine microorganisms are attractive for being as a potential resource, for a variety of chemically interesting and biologically significantly secondary metabolites have being purified from marine environments and marine microbial secondary metabolites. Mangroves are special woody plant communities in the intertidal zone of tropical and subtropical coasts. They are proved to be a natural microorganisms and new metabolites storage, and are worth of well investigating.Supported by the National High Technology Research and Development Program of China and the National Natural Science Foundation of China, we studied two endophytic fungi dothiorella sp. (HTF3) and Pestalotiopsis microspora (HTF5) collected from mangrove plant Avicennia marina at the estuary of Jiulong River, Fujian Province. It's the first time to get such two genera of fungi from mangrove trees. We replicated the whole DNA of HTF3 and got its ITS sequence for the frist time. The two endopytic fungi were fermented and their culture broth was extracted with ethyl acetate (EtoAc). The extracts were subjected to column chromatography on silica gel and HPLC. The two endophytic fungi afforded ten compounds which structures were elucidated by ESI 1D- and 2D-NMR spectra.Five compounds were isolated from the fermentation broth of HTF3, four of them were identified as novel compounds:2-[3',5'-dihydroxy-2'-(7'-hydroxy-octanoyl)-phenyl]-acetic acid ethyl ester (dothiorelone A), 2-[3',5'-dihydroxy-2'-(6'-hydroxy-octanoyl)-phenyl]-acetic acid ethyl ester (dothiorelone B), 2-[3',5'-dihydroxy-2'-(8-hydroxy-octanoyl)-phenyl]-acetic acid ethyl ester (dothiorelone C) and 6,8-dihydroxy-l-(5-hydroxy-hexyl)- isochroman- 3-one (dothiorelone D), together with a known cytosporone B (dothiorelone E), which was separated from mangrove endophytic fungi metabolites for the first time. Their structure skeletons were very rare in natural products. They all had antitumor activities, while dothiorelone E was more interesting, for it showed the highest activities, its ICso values were 4 u g/mL and 0.0625 u g/mL against human epidermal carcinoma of oral cavity, KB cell line and human Burkitt's lymphoma, Raji cell line, respectively. Furthermore, it showed broad activities against fungi, the MIC against Candida albicans Aspergillus niger Trichoderma sp. and Fusarium sp were 0.156mg/mL 0.125mg/mL 62.5 U g/mL and 62.5 u g/mL, respectively. It was high-yielded (10mg/L) and was potent for further research. We also analyzed the structure-activity relationships of these analogs.Three phenolic compounds, 4-hydroxy-benzoic acid 2,5-dihydroxy- benzal dehyde and 2,5-dihydroxy-benzoic acid, accompanied with two lipids were purified from the fermentation broth of stain HTF5. It's the first time to get such phenolic metabolites from a mangrove endophytic fungus.Our study indicated that mangrove endophytic fungi were great resources for new fungi and new structural metabolites with bio-activities. They are worth further researches.