| As an important part of marine microorganism, marine fungi have complex genetic background and high yield of secondary metabolites with rich chemical diversity and play an important role in the discovery of lead compounds, oil degradation and restoration of the marine environment, etc. In the recent years, with the deepening of research on the terrestrial microbial natural products, the discovery of new entities from these microorganisms is increasingly difficult due to chemical redundancy. As a result, many natural product chemists turned their attention to marine counterparts especially marine fungi that are supposed to be a tremendous resource for drug discovery for their special niches.With this trend in mind and as a continuation of our previous investigations on structurally new and bioactive natural products of marine fungal origin, chemical screening and bioactive screening methods were carried out inorder to study the bioactive secondary metabolite from marine fungi. The studies included isolation and purification of strains from marine samples, the screening and acquisition of talented marine fungus, the exploration fermentation conditions of target strains, the fermentation, extraction and purification of secondary metabolite, the identification, biological evaluation and structure-activity relationship evaluation of pure compounds.In this paper,103 strains of marine fungi and 46 strains of marine actinomycetes were isolated from 15 marine samples. Four talented strains of fungus were acquired though combinatory method of chemical screening (TLC, HPLC and HPLC-MS) and bioactive evaluation (cytotoxic, antibacterial, antiviral and a-glucosidase inhibitions activities). The large-scale fermentation followed by extraction was performed after the optimum fermentation conditions were found. Finally, the structure and bioactivities of pure compounds were studied systematicly.Basing on TLC, silica gel column chromatography, Sephadex LH-20 and semi-preparative HPLC, eighteen compounds (1-18) were isolated from Phoma sp. OUCMDZ-1847, including three new thiodiketopiperazines (1-3), ten known thiodiketopiperazines, two known diketopiperazines, one benzene derivative, one indole derivative and one purine derivative. Twenty three compounds (19-41) were isolated from Aspergillus sp.OUCMDZ-1583, including eighteen new conpounds (19-37) and five known ones (37-41). Three new compounds were isolated from an unidentified fungus OUCMDZ-1635, including one alkaloid (42) isolated as an inseparable mixture of two geometric isomers, one sesquiterpene (43) and one steroid (44). Two known alkaloids (45,46) were isolated from an unidentified fungus OUCMDZ-1857. The planar structure and the absolute configuration of compounds were determined by NMR, MS, UV, IR, CD, X-ray crystallographic, and chemical methods.Finally, the pure compounds isolated were tested for anti-tumer, anti-infuenza A H1N1 virus, antibacterial and a-glucosidase inhibition activities in vitro biological activity screening model. The result showed that compounds 2,4,5,11 and 12 exhibited cytotoxicity against HL-60, HCT-116, A549, K562 and MGC-803 turner cell lines. Compounds 1,2,5,10,11,14-18, and 21-23 also showed a-glucosidase inhibitions with IC50 values of 2.36,1.65,1.30,2.37,2.70,1.36,1.54,2.21,2.26, 0.027,1.65,1.19 and 1.74 mM, respectively (acarbose as positive control, IC50 0.95 mM). In adition, Compounds 18 and 21 exhibited activity against the infuenza A H1N1 virus with IC50 values of 172.4 and 175.5μM, respectively (ribavirin as positive control, IC50 137.3/μM).In conclusion, study of secondary metabilte of four marine fungi led to the isolation of fourty six compounds, including twenty four new ones. The systematic bioactivities evaluations of these compounds revealed that five thiodiketopiperazines showed strong cytotoxic activities, thirteen compounds showeda-glucosidase inhibitions activity and two compounds exhibited activity against the infuenza A H1N1 virus. |
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