The Study On The Secondary Metabolites From Seven Strains Of Marine Fungi

In recent years, the hot spot has been focused on the much more complex marine resources because of the decrease of discovering novel bioactive metabolites from terrestrial organisms. During adapting to oceanic ecosystem, marine fungi can produce numerous secondary metabolites with unique structures, novel skeletons and varied bioactivities. So marine fungi have attracted more and more attention of the natural products chemist.In this study, the secondary metabolites of seven marine fungal strains including four endophytic strains of mangroves (HTF3, BYY-1, A-1-5-4, C-2-4-7) and three strains of marine algicolous fungi (hzla01-1, PT2, B5) were studied. Totally, 61 compounds were isolated and identified from the seven strains, including 15 new compounds, 7 compounds isolated from mangrove fungi for the first time and one compound isolated from marine algicolous fungi for the first time. The bioactivities of partial compounds were studied. New compounds D23, D28, B3 and known compound B1 exhibited significant anticancer activities, additionally, compounds B1 and B3 could induce Hela cell apoptosis by FCM analysis; Compounds B1 and B3 showed very strong antioxidant activities. New compounds hz8, hx and known compound D5 exhibited marked antimicrobial activities, indicating that these compounds have potential values in applications.The secondary metabolites of the strain HTF3 were studied and structures of 26 compounds were elucidated by extensive spectroscopic data analyses and X-ray crystallographic analysis. Five of them were new polyketides, namely D15, D23, D28, D29, d4c, named dothiorelones E-I, respectively. Compound d4e was one new sugar ester. Compounds D12, HE12 and d12a were polyketides isolated from mangrove fungi for the first time, and another compound, namely D4, was alkaloid obtained from mangrove fungi for the first time. New compounds D23 and D28 exhibited cytotoxicities agaist Raji cell with IC₅₀ less than 2μg/mL The MIC values of compound D5 against Saccharomyces cerevisiae was 1.56μg/mLNineteen compounds were isolated and identified from the strain BYY-1, including eighteen polyketides and one alkaloid. Most polyketides were C₇ tetraketides, and two C₇ tetraketides (B3 and B35) were diphenyl compounds by polymerization. B2, B3, B22, B2A and B3A were new compounds, and compounds B27 and B35 were isolated from mangrove fungi for the first time. The antimicrobe, antioxidant and anticancer activities of one new diphenyl compound (B3) and two known C7 tetraketides (B1 and B9) were studied. The results indicated that three compounds showed stronger antifungal activities and weak antibacterial activities. The DPPH radical scavenging effects of compounds B1 and B3 were notable. Compouds B1 and B3 exhibited cytotoxicities agaist Hela cell with IC50 3.3μ/mL and 3.2μg/mL, respectively; additionally, compounds B1 and B3 could induce Hela cell apoptosis by FCM analysis. The antimicrobe activities, anticancer activities and mechanisms of compounds B1 and B3 were first reported.Three polyketides (A, W1 and W2) were isolated and identified from the strain A-1-5-4. Compound A was cytochalasin H; W1 was 10-membered macrolactone; W2 was mycoepoxydiene and at present there were only two mycoepoxydiene all over the world.One polyketide (CM2) was isolated and identified from the strain C-2-4-7, and it was isolated from mangrove fungi for the first time.Five compounds were isolated and identified from the strain hzla01-1, including three new polyketides (hz8, hz14 and hx), one cytochalasin (hz7) and one sterol derivative (hz11). Two new compounds (hz8 and hx) exhibited potent antimicrobe activities. The MIC value of compound hz8 against Escherichia coli was 5μg/mL, and the MIC values of compound hx against Escherichia coli, Bacillus subtilis were 5μg/mL, 1.25μg/mL, respectively.Three compounds were isolated and identified from the strain PT2. Compound pt1 was new sesquiterpene glucoside; compound pt2a was polyketide and it was isolated from marine algicolous fungi for the first time. It was reported that compound pt2a was used as a plant growth inhibitory and a food additive, it also exhibited antimicrobial activity. Compound pt2 was hexane-1,2,3,4,5,6-hexaol.Four compounds were isolated and identified from the strain B5, including one unsaturated fatty acids, one derivative of unsaturated fatty acids and two sterols derivatives.The biosynthesis pathways of compounds D5 and B were first studied by feeding sodium acetate-2-¹³C and D-glucose-¹³C₆. The results indicated compound D5 was octaketide using acetic acid to carbon-chain assembly; compound B was tetraketide and its biosynthesis with two-carbon extension. We speculated the biosynthesis pathways of compounds D5 and B.The strains A-1-5-4, hzla01-1 and PT2 were identified by morphological and molecule biological methods. The result indicated that the strain A-1-5-4 and the strain hzla01-1 belonged to Phomopsis sp., and the strain PT2 belonged to Trichoderma sp..In conclusion, our study indicated that marine fungi were valuable resources for novel metabolites with antimicrobial, antitumor and antioxidant activities.