Chemical Structures And Biological Activities Of Secondary Metabolites From Five Marine-Alga-Epiphytic Fungi

The unique environment of the ocean makes the living organisms provide abundant resources for human beings,and natural products from the ocean are important sources of new drugs.As one of the main sources of marine natural products,marine algicolous fungi can produce secondary metabolites with novel structures and distinctive bioactivity.Alga-epiphytic fungi,as a large group of marine algicolous fungi,have significantly different metabolic pathways from those of other fungi due to special ecological niche in the marine environment,which makes their secondary metabolites become an important source of new drugs.In July 2015,forty kinds of algae were collected from the coastal zone of Yantai,and eighty-eight strains of epiphytic fungi were isolated.Five of them were selected through chemical and biological screening,including Alternaria alternata K21-1,Alternaria alternata K23-3,Trichoderma virens Y13-3,Trichoderma koningiopsis Y10-2,and Geotrichum candidum Y8-1,and the chemical structures and bioactivities of secondary metabolites were systematically studied.One hundred and fifteen secondary metabolites including twenty-two new compounds and one new natural product were isolated from the extracts of them,and their skeleton types covered terpenoids,alkaloids,diketopiperazines,anthraquinones and sterols.The antibacterial and antimicroalgal activities as well as brine shrimp lethality of these compounds were determined.The compounds were isolated by repeated column chromatography?CC?on silica gel,RP-18 and Sephadex LH-20,and preparative thin layer chromatography as well as semipreparative HPLC.Their structures were elucidated by spectroscopic methods including 1D/2D NMR,MS,UV,and IR,and by comparion of those in literature.A total of thirty-five compounds were isolated and identified from the culture of A.alternata K21-1,including six new meroterpenes and one new sesterterpene.Fifteen compounds were isolated and identified from the culture of A.alternata K23-3,including two new meroterpenes.Twenty-three compounds were isolated and identified from the culture of T.virens Y13-3,including three polyketides with a new skeleton,eight new carotane sesquiterpenes,one new cadinane sesquiterpene,and two new epipolythiodioxopiperazines.Twenty-four compounds were isolated and identified from the culture of T.koningiopsis Y10-2,and eighteen compounds were isolated and identified from the culture of G.candidum Y8-1.A preliminary evaluation on antibacterial and antimicroalgal activities as well as brine shrimp lethality of some compounds was carried out.The results showed that TV22 could remarkably inhibit P.citrea,the IC₅₀ value was 8?g/mL.Compound TK20 displayed significant activity against Pseudoalteromonas citrea,Vibrio parahaemolyticus,V.splendidus,V.anguillarum and V.harveyi with the IC₅₀ value ranging from 8 to 32?g/m L.Indole derivatives GC9?11,and sesquiterpenes TV15?TV16*showed potential brine shrimp lethality,with IC₅₀ value of 17,18,18,17 and21?g/mL,respectively.In the experiment on growth inhibition of microalgae,compounds TV1*?3*had significant inhibitory effect on Chattonella marina and Karlodinium veneficum,with the IC₅₀ value ranging from 0.41 to 1.0?g/m L.Compounds TV6*?8*,TV11*,TV15,GC9?12,TK15,TK16 and TK18 showed potent inhibitory activity against C.marina,Prorocentrum donghaiense,Heterosigma akashiwo and K.veneficum,the IC₅₀ value ranging from 0.040 to 12?g/m L.In this dissertation,secondary metabolites of five alga-epiphytic fungi were thoroughly studied,it not only enriched the research of marine natural products,supplied a new reference for the research of secondary metabolites of alga-epiphytic fungi,but provided theoretical foundation and scientific basis for development and utilization of biological resources.