Chemical Diversity And Biological Activity Of Secondary Metabolites From The Endophytic Fungi Of Laurencia Okamurai Origination In Axenic Culture And Coculture

Natural products are a historical resources of new drugs or pharmaceutical lead compounds.Marine fungi are an indispensable part of natural product research,offering various structures with potent bioactivities,due to their unique and complicated habitats.Nevertheless,rare occurrences of the novel compounds and chemical redundancy are a chronic problem in the microbial secondary metabolites chemistry.As an available way for activation of silent genes and induction of new compounds,fungal co-culture strategy has attracted more and more attentions in recent years.In continuation of our efforts to identify new bioactive secondary metabolites from marine-derived fungi,chemical investigations were performed on three strains of marine red alga Laurencia okamurai-derived fungi Talaromyces islandicus EN-501,Cladosporium cladosporioides EN-399,and Aspergillus terreus EN-539 in singlestrain culture.Moreover,we investigated the secondary metabolites from the dual-strain culture of C.cladosporioides EN-399 and the mangrove-derived bacterial Bacillus subtilis MA-288,as well as the dual-strain culture of Paecilomyces lilacinus EN-531 and A.terreus EN-539.As a result,66 compounds were isolated and identified from the above culture extracts,of which 17 were new compounds.Twelve compounds,including five new hydroanthraquinones,two new diphenylketones and two new xanthones,were isolated and elucidated from the fungus T.islandicus EN-501.Seven compounds,including five new cladosporols,were isolated and identified from the fungus C.cladosporioides EN-399.Twelve compounds were isolated and identified from the fungus A.terreus EN-539.Seventeen compounds were isolated and identified from the dual culture of C.cladosporioides EN-399 and B.subtilis MA-288,including five small molecule indoles which could be detected by the trace in the single culture of the fungus C.cladosporioides EN-399.Twenty-one compounds were isolated and identified from the dual culture of P.lilacinus EN-531 and A.terreus EN-539,including one new meroterpenoid and two new terreins which could not be detected in the single culture of both fungi.The new compouds were evaluated for their DPPH and ABTS scavenging,antimicrobial and cytotoxic activities.Compounds HT 1*-9* showed significant DPPH and ABTS scavenging activities with IC50 values ranging from 8.3 to 52 ?M and moderate antibacterial activities with MIC values ranging from 2 to 64 ?g/mL.Compounds RST 1*-RST 6* exhibited inhibitory activities against Escherichia coli,Micrococcus luteus,and Vibrio harveyi,with MIC values ranging from 4 to 128 ?g/mL.In adddition,compounds RST 2*,RST 3*,and RST 6* displayed cytotoxic activities against most of the tested cell lines: A549,H446,Hela,Huh7,L02,LM3,MCF-7,and SW1990,with IC50 values ranging from 1.0 to 20.0 ?M.Compound AP 2 showed inhibitory activity against M.luteus with MIC value of 32 ?g/mL and compounds AP 6*-AP 9 showed activities against Alternaria brassicae,Alternaria porri,Edwardsiella tarda,Physalospora piricolav,Staphylococcus aureus,with MIC values ranging from 8 to 64 ?g/m L.