Secondary Metabolites And Bioactivties From Two Deep-Sea-Sediment Derived Fungi

Unusual marine environments,such as high pressure,low temperature,anaerobic,high salt,no light,oligotrophic,and high halogen,are associated with chemical diversity,leading to a resource of novel active substances for the development of bioactive products.Finding new natural products in marine fungi,particularly those living in deep-sea and special marine enviroments is an important approach to indentify novel active agents.System studied on the ssecondary metabolities form two deep-sea sediments derived fungi Penicillium sp.SCSIO Ind16F01 and Aspergillus sp.T7-1 and their bioactivities were carried out.Twenty-seven compounds were isolated from the fungus Penicillium sp.S CSIO Ind16F01,and 17 compounds were identified as:1,6-dihydroxy-7-methyl-9-oxaindole-5-carboxylic acid methyl ester(P1),coniochaetone J(P2),8-hydrox y-6-methyl-9-oxo-9H-xanthene-1-carboxylic acid methyl ester(P3),1,3,8-trihydro xy-6-hydroxymethyl hydrazine(P4),coniochaetone B(P5),citrinolactones B(P 6),epiremisporine B(P7),quinolonimide(P8),quinolactacins B(P9),quinolact acin C1(P10),quinolactacin C2(P11),quinolactacin A1(P12),quinolactacin A2(P13),di(2-diethylhexyl)terephthalate(P14),parahydroxybenzoic acid(P15),ergosterol peroxide(P16),5a,8a-peroxo-(22E,24R)-ergoline-6,22-diene-3?-alcoho 1(P17).Their sturctures include seven polyketones(P1-P7),six alkaloids(P8-P13),two ergosterols(P16-P17)and two small molecules(P14-P15).Compoun ds P1 and P2 were the first reported new compounds.Forty-one compounds were isolated from the fungus Aspergillus sp.T7-1,and 21 compounds were identified as:N-(2-hydroxy-4-methylpentyl)acetamide(Al),4-hydroxy-3-(2-methylpropyl)-benzoic acid(A2),2-hydroxy-5-isobutyl-3-P ropanamidylpyrazine(A3),versiol(A4),decumbenone B(A5),3,3'-dihydroxy-5,5'-dimethyldiphenylether(A6),versiconol(A7),notoamide B(A8),notoamide C(A9),brevianamide F(A10),altemaroside B(All),(5S,6R,7S,8R)-5-amino-(2 Z,4Z)-1,2,3-trihydroxybuta-2,4-Dienyloxy-pentane-6,7,8,9-tetraol(A12),kipukasin E(A13),kipukasin D(A14),kipukasin H(A15),kipukasin I(A16),2'-deoxyth ymidine(A17),2'-deoxyuridine(A18),uridine(A19),deoxyadenosine(A20),ce revisterol(A21).Their structures include three amides(Al,A3,All),two ses quiterpenes(A4-A5),three polyketones(A2,A6,A7),three indole alkaloids(A 8-A10),eight Nucleosides and nucleoside derivatives(A13-A20),one sterol(A 21),In addition,Compound A1 and A2 are new natural products.On the base of the sturtures of compounds and references,these compounds were tested by anti-bacterium,cytotoxic activities.The results showed that compounds P2 and P7 exhibited weak inhibitory activity against EV71 in vitro,with IC50 values of 81.6 and 19.8?M.In addition,compound P7 also exhibited cytotoxic effects on the tested cancer cell lines(K562,MCF-7,and SGC7901)with IC50 values of 16.6,16.3,and 15.8?M,respectively.Compound A13 exhibited a certain inhibitory activity against proliferation of hepatic stellate cells at a concentration of 23.7?M.The above results indicate that deep-sea fungus has the potential to produce novel and biologically active substances,and could provides marine-derived lead compounds for the development of novel antiviral,antitumor and anti-fibrotic drugs.