Study On The Metabolites Of Four Marine Mangrove Endophytic Fungi

Marine mangrove endophytic fungi have their own unique metabolic pathways due to their special growth environment.Among their metabolites,they have shown a ability to produce a large number of structurally novel and medicinally active metabolites,which have enormous potential for development.In this paper,the chemical composition of the secondary metabolites from the four endophytic fungi Fusarium sp.R5,Penicillium chrysogenum V11,Nigrospora sphaerica ZMT01 and Peniophora sp.M2 were studied.These four strains in solid medium were extracted with ethyl acetate and n-butanol respectively,and 36 compounds were isolated by a variety of separation and purification methods including silica gel column chromatography,sephadex LH-20 column chromatography,thin layer chromatography,HPLC and recrystallization.The structures of these compounds were identified mainly by analysis of NMR,HRESIMS,IR,UV spectra,as well as by comparision with literatures.The results are listed as follows:Twelve compounds were isolated from the endophytic fungus Fusarium sp.R5.They were fusarihexin A(1),fusarihexin B(2),cyclo-(L-Leu-L-Leu-D-Leu-L-Leu-L-Val)(3),cyclo-(L-Leu-L-Leu-D-Leu-L-Leu-L-Ile)(4),3-phenyl-1-cyclopenten-2-one(5)2-hydroxy-3-phenyl-1-cyclopenten-2-one(6),carotenoid(7),tempeh-7,22-diene-3?,5?,6?-triol(8),L-arabitol(9),p-hydroxybenzoic acid(10),L-mannitol(11),tetradecanoic acid(12).Fourteen compounds were isolated from the endophytic fungus Penicillium chrysogenum V11.They were penochalasin K(13),penochalasin I(14),N-fumaryl-L-alanine dimethyl ester(15),N,N'-2-[(S)-1-methoxycarbonylethyl]-fumaramide(16),chaetoglobosin C(17),chaetoglobosin F(18),chaetoglobosin A(19),?-sitosterol(20),3?-cholest-5-en-3-ol(21),ergoquinone-4,6,8(14),22-tetraen-3-one(22),sohirnone C(23),chrysogin(24),methyl glucoside(25),uracil(26).Five compounds were isolated from Nigrospora sphaerica ZMT01,including nigrosporamide A(27),4-prenyloxyclavatol(28),clavatol(29),polybotrin(30),5-hydroxymethyl-2-one furaldehyde(31).Five compounds were isolated from the endophytic fungi Peniophora sp.M2,including ergosterol peroxide(32),thymidine(33),3,5-pyrimidine-2,4-(1H,3H)-dione(34),1,5-dimethylpyrimidine-2,4(1H,3H)-dione(35),sch725674(36).Among these,compounds 1,2,13,15,27 and 28 are new molecules.Compound 1 is the first cyclohexadepsipeptide that has four phenylalanine residues.Compound 7 was isolated from Fusarium sp.for the first time.Compounds 16,23,24 and 25 were isolated from Penicillium chrysogenum for the first time.Then,the antibacterial activity,enzyme inhibitory activity and cytotoxic activity of some of the isolated compounds were examined.In the antifungal activity assay,the MIC values of 1,2,5,6,13,23 and 27 against certain plant pathogens are good,suggesting that they have potential for the development of agricultural antibiotics.In vitro cytotoxicity of compound 13 against breast cancer cell line MDA-MB-435,human gastric cancer cell line SGC-7901 and human lung adenocarcinoma epithelial cell line A549 was tested by MTT assay.It shows strong cytotoxic activity against the three cell lines,suggesting that it can be used as an anti-tumor lead compound for in-depth research.In the enzyme inhibitory activity assay,compound 27 shows a high inhibitory activity against ?-glucosidase,suggesting that it can be expected to become a drug for treating diabetes.In conclusion,this study led to the isolation of six new and thirty known compounds.Some of them exhibited good activity,which provided the basis for further applied research.