Studies On The Secondary Metabolites Of Three Marine Actinomycetes

Marine microorganisms may have unique secondary metabolic pathways which aredifferent from that on land because of the unusual living environment. In recent year, withthe discovery of more and more novel bioactive secondary metabolites from marinemicroorganisms, they have been considered the most prospective sources in the field ofdrug development. And marine actinomycetes have draw the most attention because ofthe good harvest of active compounds. And nitrogenous compounds as an important part ofnatural compound from marine microorganisms take the most percent in active compounds,so they have great influence on drug development.In order to get novel bio-active nitrogenous metabolites from marine-derivedactinomycetes, the actinomycetes isolated from marine sediments samples were screenedusing the chemical and biological activity screening phases. In this process of chemicalscreening phase, TLC and HPLC-UV-MS were used. And the chemical diversification andnitrogenous were the objectives for study. In this process of biological activity screeningphase, it was focused on antiviral (H1N1), antimicrobial (Staphylococcus aureus andCandida albicans), and anti-tumor (MCF-7cell line) activities. By the comprehensiveanalysis of the chemical and biological results, two target strains have been selected forfurther study. And a novel genus of actinomycetes isolated from the mangroves plant hasbeen choosed for research.Firstly, the fermentation conditions of target strains were optimized including medium,pH and so on according to the strains source. The whole broths were extracted with ethylacetate to give ferment extracts after the fermentation of the three marine-derivedactinomycetes strains. Then the extracts were subjected to extensive columnchromatography and HPLC to give pure compounds. And39compounds were obtained.Compound1,2,2d and5-9were got from Streptomyces pratensis OUCMDZ-3159.Compound10-25and compound26-41were obtained from Jishengella endophyticaOUCMDZ-4441and Streptomyces sp. OUCMDZ-1351, respectively.By means of modern spectral analysis such as MS, NMR, UV, IR, CD, OR, X-rayquantum chemical calculations and chemical reactions, the structures of39compouds weredetermined. And there are9new compouds. The new compounds include three types,amide (1,2d,6), pyrazine alkaloids (10) and diketopiperazine derivatives (26,27,29,30,33). The antiviral and antimicrobial activities of these compounds were evaluated.Compound1and2showed modest antimicrobial activity against Candida albicans withMIC values of10μM and16μM， reseparately. And compound1showed antioxidantactivitiy against DPPH with the IC50value of122μM. Compound28and31showedpotential antiviral activity against H1N1with the IC50values of6.8±1.5and28.9±2.2μM.And12,17,19,22and29showed modest antiviral activity against H1N1with the IC50values of39.7(±5.6),38.3(±1.2),25.0(±3.6),45.9(±2.1)μg/mL and41.5±4.5μM,respectively.And the factors which influence the structural stability of2were investigated. Thenthe possible reaction mechanisms of2with light, temperature and oxygen were expounded.During the research, two novel compounds, compound3and4were got. According to theresult of the research, the absolute configuration of2has been determined firstly with themethod of X-ray copper target single crystal diffraction.