Chemical Investigation And Biological Activity Evaluation Of Six Marine Organisms

Marine organisms(invertebrates,microbes,and plants)are important sources of marine active secondary metabolites and one of the important sources of new medicines In the process of our searching for biologically active secondary metabolites,this paper conducted a chemical investigation of two deep-sea sediments derived actinomycetes,and four marine invertebrates(two corals and two sponges)collected off South China Sea.Besides,the biological activities of the isolates were also evaluatedUsing a variety of column chromatography separation methods,a total of 70 compounds were isolated and identified from the above six marine samples.The structures involves peptides,sesquiterpenoids,nor-sesquiterpenoids,diterpenoids,alkaloids and other structural types.Of these compounds,15 new compounds and 1 new natural product were identified.Their structure and stereochemistry were elucidated on the basis of extensive spectroscopic analysis and chemical methods,and by comparison of the data with those reported data in the literature.Some of them were found to show significant bioactivities on specific bioassay models.This study not only enriches the theoretical basis of marine natural product research,but also provides a scientific basis for further development and application of the medicinal value of marine natural products1)In the screening of novel compounds from two deep sea-derived actinomycetes,the production of different metabolites was regulated by changing the culture conditions A novel siderophore named albisporachelin(2-1)was isolated from a deep-sea sediment-derived actinomycetes Amycolatopsis albispora WP1T,which was the first siderophore-type compound from marine Amycolatopsis.The new siderophore is also the first natural product derived from the new actinomycete A.albispora.The production of secondary metabolites from another deep-sea sediment-derived actinomycete Streptomyces sp.YB104 was screened based on the different cultivation condition.Strain YB104 could produce biologically active inthomycin compound named inthomycin B(2-2)under oligotrophic conditions.This is the first report that a potential engineering strain Streptomyces sp.YB104 is discovered to produce inthomycin-like compounds with high yield(25 mg/L).Also,inthomycin-based compounds were obtained from the ocean for the first timeIn the study of the chemical investigation of two soft corals(Lemnalia flava and Sinularia flexibilis)collected from the South China Sea,52 compounds were isolated,12 of which were new compounds.Among them,xishaflavalin F(3-1)represents an uncommon sesquiterpenoid skeleton containing a rare nine-membered ring lactone and the AC of compound 3-1 was unambiguously determined by XRD analysis.In addition,four new nardosinane-type sesquiterpenoids were identified.In fact,nitrogen-containing sesquiterpenoid are rarely found in nature,xishaflavalin D(3-4)is a rare nitrogenous secondary metabolite from soft corals of genus Lemnalia and the first example for nitrogen-containing nardosinane-type sesquiterpenoid.Besides,xishaflavalins B and C(3-2 and 3-3)represent the only peroxide bridge containing secondary metabolites from Lemnalia.This study also successfully applied a variety of computer-assisted structural elucidation strategies,including residual dipolar coupling(RDC),calculation of carbon spectrum,TDDFT-ECD(time-dependent density functional theory electronic circular dichroism calculation)quantum chemical calculation method.The relative configuration and absolute configuration of compounds with complex chiral centers were determined In addition,the absolute configuration of three sesquiterpenoids including xishaflavalin F(3-1),paralemnolin R(3-6),pathylactone A(3-26)and two diterpenoids diepoxycembrene A(4-39)and 11-epi-sinulariolide acetate(4-48)were determined based on the XRD analysisSome of the diterpenoids and/or sesquiterpenoids isolated from these two corals possess significant anti-inflammatory activity and cytotoxic activity.Compounds(3-20,3-22,3-24,3-27,and 3-30)isolated from L.flava and compounds(3-41,3-40,3-48,3-41)from S.flexibilis showed in vitro anti-inflammatory activity with IC50 values ranging from 1.0 μM to 6.8 μM,which were superior to the positive control(dexamethasone,IC50 = 8.7 μM).Besides,compounds 3-45 from soft coral S.flexibilis showed strong cytotoxic activity(IC50 = 8.93-27.39 μM).Through the comparison of the structure and biological activity of diterpenoids from S.flexibilis,the primary structure-activity relationship(SAR)of some diterpenoids was analyzed3)In the study of the chemical constituents of two sponges collected off Xidao Island,South China Sea,a total of 16 compounds were isolated and identified,two of which were new compounds and one was new natural product.Among them,the new compound neopetroside(4-1)from sponge Neopetrosia sp.is a rare pyridine nucleoside alkaloid compound.This study is the second report of compound 4-1,a novel alkaloid bearing the extremely rare α-N-glycoside linkage,from nature origin.The new kalihinane-type diterpenoid named xidaoformamide A(4-9)from sponge Acanthella cavernosa is the the second diterpenoids with two formamide structural units found in nature.Besides,the absolute configuration of a known sesquiterpenoid named axiriabiline A(4-13)was determined based on the XRD analysis.The results of bioactive assay showed that only the known compound jaspamide(4-16)showed significant cytotoxic activity(IC50=97-412 nM).This research was the first report of the PKS-NRPS hybrid compound jaspamide was found from the Acanthella sponge.