A Research On Secondary Metabolites And Biological Activity Of Marine Fungus Penicillium Rubens YFJ-4

The unique ecological environment of the ocean makes marine fungi have different metabolic regulatory pathways from other sources of fungi,and deep-sea fungi are more likely to produce secondary metabolites with novel structures and significant activity,which have great potential in drug development,and some of the active products have been developed into drugs for clinical use,therefore mining drug molecules with potential biological activity from marine biological resources has become a hot spot for pharmacological research.In this study,Penicillium rubens YFJ-4 was selected for comprehensive activity screening and chemical composition screening,and the phosphodiesterase andα-glucosidase inhibitory components were proposed to be explored in depth.Various chromatographic techniques（silica gel,ODS C-18,HPLC,gel）were used to isolate and purify the ethyl acetate extract from the solid fermentation of this strain of rice to obtain the monomeric compounds.Various chromatographic techniques（silica gel,ODS C-18,HPLC,gel）were used to separate and purify the ethyl acetate extract from the solid fermentation of rice by the bacterium,and the monomer compound was obtained.Modern spectroscopic techniques such as nuclear magnetic resonance spectroscopy(¹HNMR,¹³CNMR,2DNMR),high resolution mass spectrometry（HRESIMS）,ultraviolet spectroscopy（UV）,circular dichroism（CD）and X-Ray single crystal diffraction were used to determine the structure of the monomeric compounds including absolute conformation.A total of 30 monomeric compounds were identified from strain Penicillium rubens YFJ-4,including talarolutin-type heteroterpenes（1～4,7～9）,andrastin-type heteroterpenes（23～27）,cyclic alkenoid diterpenes（28～30）,steroids（19～21）,chromogenic ketones（13,14,16,17）,anthraquinones（15）and other structural types.Five new compounds（1～5）,among which talarolutins E-H（compound 1～4）,a rare class of heteroterpenes,were isolated from deep-sea fungi for the first time,and the structure of this class has a unique linkage between the drimane type sesquiterpene fragment and the pyrone fragment This class of structures has a unique linkage pattern between trimane type sesquiterpene fragments and pyrone fragments,which enriches the structural diversity of this class of heteroterpenes.This study evaluated the antioxidant,phosphodiesterase Ⅳ（PDE4）inhibiting andα-glucosidase inhibiting activities of some compounds,as well as their inhibitory effects on the proliferation of three tumor cell lines（HeLa,MCF-7,786-O）.The results showed that compound 10 exhibited inhibitory activity againstα-glucosidase with an IC₅₀of 29.2μM.Compounds 14 and 15 exhibited phosphodiesterase Ⅳ inhibitory activity with IC₅₀values of 7.8,8.3μM.The binding mode of the active compounds to the PDE4B protein was analyzed using molecular docking simulation software to study the interaction with the receptor and predict the optimal binding mode.None of the tested compounds showed significant antitumor activity.This thesis presents a brief review of the diversity and biological activity of secondary metabolites of Penicillium fungi of marine origin.The secondary metabolites of the marine fungus Penicillium rubens YFJ-4 were investigated,and the novel talarolutin-type heteroterpenes identified from them added to the family of this class of compounds,providing an important reference for the structural identification of this class of compounds and enriching the diversity of chemical structures of natural products by speculating the biogenic pathways for this type of compounds.Active compounds 14 and 15provided structural information for the development of efficient and low-toxic PDE4 inhibitor anti-inflammatory drugs.