Studies On The Bioactive Secondary Metabolites Of One Sponge-derived Fungus

As simple multicellular invertebrates and filter feeders, sponge are rich of a large number of microorganisms on the surface and in the body. Due to unique living environment, sponge fungi which form unique and variety biosynthetic pathway in the long-term natural selection process, can generate many secondary metabolites with structural novelty and biological activities. Therefore, sponge-derived fungi become an important resource for lead compounds of drugs and hot spot in the research of marine bioactive substances. In order to search for new bioactive compounds, sponge derived fungi were isolated from 22 sponges collected from South China Sea, secondary metabolites of 1 sponge derived fungal strain were studied, and the antitumor and anti-H1N1 activities were also tested.98 fungi were isolated from 22 marine sponge samples collected from Xisha South China Sea. Using cytotoxicity assay and P388 cell line as bioactive screen model,25 fungal strains were detected the cytotoxic activity. Together with chemical screen assays by TLC and HPLC methods, one strains, Aspergillus aureolatus HDN14-107was chosen as aimed strains for further study.In all,16 compounds were isolated and purified, from the extracts of the 2 strain, by using solvent extraction, silica gel column, ODS, Sephadex LH20, MPLC, HPLC and etc. Basing on their physicochemical properties and spectral data (IR, UV, MS, NMR, and CD), combined with quantum chemical CD calculation, structures of the 16 pure compounds were respectively determined. Among them there are 3 new austalides compounds.The antitumor activities of compounds 1-16 were determined using MTT and SRB methods, indicated that compound 4 have widespread strong activities against Hela. HL-60 and K562 cell with IC50 values 27.45,32.33 and 40.21 μM, respectively. The H1N1 replication inhibition activities were evaluated on compounds 1-16. The results showed that compounds 3 and 5 has obvious activity with the inhibition ratio of 60.6% and 51.5% respectively, and compounds 9 and 15 has moderate activity (35.7%,38.4%) against H1N1.Summarily,98 fungi were isolated from 22 sponge samples, and 16 compounds were isolated and identified from 1 sponge-derived fungal strain, including 3 new austalides compounds. The antitumor activities of austalides compounds were evaluated using 5 human tumor cell lines and the H1N1 replication inhibition activities were first reported.The study provides a chemotype for natural product research and the search for lead compounds of antitumor and anti-H1N1 drugs. This results showed that the sponge-derived fungus have diverse metabolites and bioactive which are important medicinal microbial resources worthy for further research.