Study On Secondary Metabolites Of Marine-derived Fungi From Xinglin Bay Of Xiamen And Their Biological Activities

The abuse of antibiotics in humans has led to the emergence of high-level and multi-drug resistant pathogens,thus the development of new active compounds is urgently needed for drug discovery.72 strains of marine-derived fungi were obtained from rhizosphere mud and water samples around mangrove collected from Xinglin Bay,Xiamen,Fujian Province,China.The crude extracts were extracted with ethyl acetate after fermentation.By using Staphylococcus aureus,Escherichia coli,Helicobacter pylori and Candida albicans as indicator bacteria,high-throughput activities screening were performed on crude extracts and the minimum inhibitory concentration of crude ethyl acetate extracts were used as a reference,HPLC fingerprint analysis was used to eliminate duplicates.Five strains of fungi with abundant secondary metabolites and antibacterial biological activity were identified as potential strains for future chemical investigation.MF180246 and MF180262 were performed large-scale fermentation and chemical constituents studies.The crude extracts were separated and purified by reduced-pressure normal phase silica gel column chromatography,Sephadex LH-20 gel column chromatography,and high performance liquid chromatography.The structures of the compounds were determined by mass spectrometry(MS),nuclear magnetic resonance(NMR),ultraviolet spectroscopy(UV),experimental and calculated circular dichroism(CD)spectroscopy,optional rotation(OR),and the compounds were tested by microbroth dilution method for biological activities.19 compounds were obtained from the marine-derived fungus MF180246,which were identified as asperbrunneo acid(1),secalonic acid H(2),secalonic acid D(3),secalonic acid F(4),secalonic acid F1(5),penicillixanthone A(6),chrysoxanthone C(7),asperdichrome(8),herbarulide(9),emodin(10),tetrahydrofuranlactone derivative(11),aspergillusol A(12),3,4-dihydroxy-benzeneacetic acid(13),4-hydroxybenzaldehyde(14),2-(4-hydroxyphenyl)-ethanol(15),vanillic acid(16),3,4-dihydroxybenzoic acid(17),2,5-dihydroxyphenylacetic acid methyl ester(18),1-phenyl-1,2-ethanediol(19).Compound 1was a novel natural product possessing new carbon skeleton.13 compounds were obtained from the marine-derived fungus MF180262,which were identified as 3-(5-methoxycarbonylpentyl)-4-methylfuran-2,5-dione(20),and two dimeric hexylitaconic acid derivatives(21 and 22),together with ten known compounds,kotanin(23),fonsecinone A(24),asperpyrones B(25),aurasperone A(26),asperpyrone C(27),desertorin B(28),pyrophen(29),orlandin(30),aspernigrin A(31)and asperitaconic acid B(32).Compounds 20,21 and 22 were new compounds.Compounds 21 and 22 were the first discovered dimeric hexylitaconic acid derivatives.Compounds 24,26 and 27 showed moderate antibacterial activities against Helicobacter pylori with minimum inhibitory concentration(MIC)values of 16 ?g/mL.