Identification And Bioactivities Of Secondary Metabolites From Penicillium Spp. Collected From The Bohai Sea

Since the Italian professor Giuseppe Brotzu isolated cephalosporins from C.acremonium in 1940,marine fungi have become an important research target for the screening of drug leading compounds.For decades,a large number of secondary biometabols with good biological activity have been isolated from marine fungi around the world.China’s marine fungi are widely distributed.However,most of the research on secondary metabolites of marine fungi in China is concentrated on the South China Sea and the East China Sea.As the only semi-enclosed inland sea in China,Bohai Sea has a stable hydrological environment and fertile water.This provides a good living condition for fungi and also has a material basis for producing abundant secondary metabolites.In this study,the fungi Penicillium polonicum and Penicillium janthinellum were investigated.The optimization of fermentation conditions of P.polonicum was discussed.By screening carbon sources,nitrogen sources,changing osmotic pressure and adding epigenetic modifiers,it was finally determined that the metabolic mode of fungi could be successfully changed by adding epigenetic modifiers,and several new quinazoline alkaloids were obtained succesfully.In order to obtain secondary metabolites,natural product separation methods such as forward and reverse silica gel column chromatography,Sephadex LH-20,MPLC and semi-preparative reversed phase HPLC were used.NMR,MS,IR,UV,ECD methods were used for identification.There were 33 compounds isolated and identificated,including 7 quinazoline alkaloids,6 steroids,6 benzodiazepine alkaloids,4 diphenyl ethers,2 indole alkaloids,2 dilute compounds and 4 other compounds.Compunds 1 and 2 represent the first examples of steroids forming a five-membered lactone between C-23 and C-27 from marine fungi.Their absolute configurations were determined by DP4+ method.The C-18 epimer of aurantiomide C(26)and the C-3 epimer of the anacine(27)compound were isolated and identified for the first time.Their absolute configuration was determined by quantum chemical calculation of ECD.The new compounds 1 and 2 showed a weak inhibitory effect on part of the marine Vibrio..Compounds 3 and 5 showed weakt inhibition of some bacteria.Compound 12 and 27 exhibited cytotoxic activity against some cancer cells.