Study On Metabolites Of Active Fungi From Three Strains Of Sponge In Beibu Gulf

Objective:In this paper,a series of monomer compounds were isolated and identified by modern spectroscopic techniques（NMR,IR,MS,etc.）,and combined with traditional methods,based on the interdisciplinary disciplines of microbiology,natural pharmaceutical chemistry and chemobiology,which provided scientific accumulation for in-depth exploration of the structural diversity of secondary metabolites from Marine microorganisms.The activity evaluation and structure-activity relationship of secondary metabolites of sponge-derived fungi were conducted to provide a theoretical basis for the study of abundant marine natural active substances.Methods:Three dominant strains were selected from the one hundred and thirteen strains of the fungus that derived from the sponge of the Beibu Gulf by means of parallel three-group small-batch fermentation in rice test tube medium,combined with chemical composition analysis and preliminary screening of antibacterial activity.The three strains were fermented in large batches and obtained the crude extracts.The chemical structures of the monomeric compounds were using silica gel column chromatography,high performance liquid chromatography（HPLC）and other chemical separation methods,and that identified by nuclear magnetic resonance（NMR）,infrared spectrometer（IR）,mass spectrometry（MS）and circular dichroism（CD）.The monomeric compounds were tested for the antibacterial,toxic,enzymatic and NF-κB luciferase activities of prostatic cancer cells.Results:Sixteen monomer compounds were isolated from the secondary metabolites of strain Penicillium sp.SCSIO 41413,of which three were new compounds（1～3）,including a new quinazoline diketopiperazine compound（1）,a new alkaloid natural product（2）and a new butenolide compound（3）,and thirteen known compounds（4～16）.The preliminary screening showed that compounds 3 and 12 displayed significant inhibitory activity against PI3K protein,with IC₅₀values of 1.7μM and 9.8μM,respectively.The molecular bonding of phenolic hydroxyl group of 3 with residues THR887,TYR867 and ALA885 was found.The ester group interacts with VAL882 by hydrogen bonding.The phenolic hydroxyl groups in compound 12 form three hydrogen bonds with residues THR887,TYR867 and ASP950.Compounds 3and 15 were showed inhibit LPs-induced NF-κB activation in RAW 264.7cells.Nine compounds were isolated from the fermentation products of strain Roussoella sp.SCSIO 41414,including a new alkaloid compound（17）and eight known compounds（18～25）.Six compounds（26～31）were isolated from the secondary metabolites of strain Cladosporium sp.SCSIO 41415.Conclusions:In this paper,one hundred and thirteen strains were isolated from sponge samples from Beibu Gulf by repeated microbial test.Three target strains were selected by combining composition analysis and preliminary screening of activity,and thirty-one monomer compounds were isolated by large-scale fermentation in rice medium.The above research provides a scientific basis for further exploration of marine medicinal microorganism resources in the Beibu Gulf.