Chemodiversity And Bioactivity Of Sulfur-and/or Nitrogen-containing Secondary Metabolites From Marine-derived Fungi

It is generally recognized that microorganisms living in unusual or specialized eco-systems may increase the chance to produce structurally unique and biologically active compounds.Marine microorganisms not only evolve unique metabolic pathways for the special living environment in the oceans,but also be environment friendly.The capability of marine microorganisms to produce highly potent and structurally interesting metabolites has attracted much interest to discover marine natural products with pharmaceutical application potential.In our efforts to identify new bioactive secondary metabolites from marine-derived fungi,we investigated secondary metabolites of five strains of the fungal Penicillium sumatrense MA92,Penicillium bilaiae MA267,Eurotium rubrum MA150,Penicillium brocae MA231,and Cladosporium cladosporioides MA263.Moreover,we performed chemical investigations on the co-culture of Beauveria felina EN135 and Penicillium citrinin MA197.As a result,130 compounds were characterized from culture extracts of the fungi above,and 37 of them were new structures.Most of the compounds were assayed for the cytotoxic,antimicrobial,and DPPH scavenging activities,seven structures with sulfur atoms showed strong cytotoxicity against some of the tested tumor cell lines.Fifteen compounds were isolated and elucidated from the fungus P.sumatrense MA92,including three new sulfur-containing curvularin derivatives and one new macrolide.Thirty-seven compounds were isolated and identified from the fungus E.rubrum MA150,three of which were new indolediketopiperazine alkaloids and three new polyketones.Thirty-two compounds were isolated and identified from the PDB medium culture extract of the fungus P.brocae MA231,including sixteen new structures,while seven compounds from the Czapek agar with three new ones of them.Sixteen compounds were isolated and elucidated from the fungus P.bilaiae MA267,including four new sesquiterpenes.Thirteen structures were isolated and identified from the fungus C.cladosporioides MA263,including two new compounds.Sixteencompounds were isolated and identified from the co-culture of B.felina EN135 and P.citrinum MA197,two of which were new polyketone derivatives.The isolated compounds were examined for cytotoxicity,antimicrobial,DPPH radicals scavenging activities as well as brine shrimp lethality.Compounds SU1*~3*displayed cytotoxic activities against seven tumor cell lines(Du145,Hela,Huh 7,MCF-7,NCI-H460,SGC-7901,SW1990),with IC50 values ranging from 3.8~10 ?M,while compounds BO1*~2*and BO5*~6* showed cytotoxic activities against nine tumor cell lines(Du145,Hela,HepG2,MCF-7,NCI-H460,SGC-7901,SW1990,SW480,U251),with IC50 values ranging from 0.89~9.0 ?M.Notably,compounds BO1* and BO2* exhibited potent activity against the SW480 tumor cell lines,with IC50 values of 2.0 and 1.2 ?M,respectively,while compound BO6* showed strong activity against the DU145 and NCI-H460 cell lines,with IC50 values of 2.0 and 1.2?M,respectively.In the antimicrobial screening,compounds BO8*~12* and BI1*~2* showed potent activities against Staphylococcus aureus,Micrococcus luteus and Colletotrichum gloeosporioides,with MIC values ranging from 0.25~8.0 ?g/mL.The research provided abundant theoretical basis and resource for developing and utilizing the marine-derived fungi.Seven new compounds with sulfur atoms in their structures exhibited strong cytotoxic activities against some of the tested tumor cell lines and two sesquiterpenes with rarely described2,6,9-trimethyl-tricyclo[6.3.1.01,5]dodecane skeleton displayed strong activity against Colletotrichum gloeosporioides,indicating potential development and application prospect.