Discovery And Preliminary Screening Of Natural Products Against Tumor And Diabetes From Fujian Coastal Fungi

Marine fungi secondary metabolites are diverse,structurally specific,and biologically active,and have become an important source of medicinal lead compounds,which are favored by more and more researchers.In this paper,the fungi from the coastal areas of Fujian Province were studied,and the secondary metabolites were obtained by large-scale fermentation,isolation and purification,and them anti-tumor activity research,was carried out to screen out the active pharmaceutical lead compounds.The research ideas are as follows:First:Two active marine fungi（Penicillium oxalicum and Penicillium citrinum）were selected from the active strain pool independently created by our research group,and they were fermented on a large scale,using ethyl acetate and acetone respectively.The extract is extracted three times,and the extract is concentrated and distilled under reduced pressure to obtain two parts of mycelium and fermented extract,which are separated and purified by gel column chromatography,silica gel column chromatography,thin layer chromatography,and semi-preparative high performance liquid chromatography.By the method,a single compound was obtained,and four natural products were isolated from the fungus（Penicillium oxalicum）fungus,and five natural products were isolated from the fungus（Penicillium citrinum）fungus.Second:the compounds were identified by means of nuclear magnetic resonance,mass spectrometry,infrared,ultraviolet,etc.and compounds 1-5 were found to be new compounds.Their antitumor activities were identified by MTT assay.The results showed that compound 1 had strong antitumor activity against Hela,HCT116,MCF-7,Hep-3B,A549 and Hela/VCR cells,and the IC₅₀was 3.2,6.1,and 9.2,respectively.19.3,36.7μM;Compound 2 has an IC₅₀of 4.5,5.4,4.5,12.1,6.3,and 4.8μM for the above cells;Compound 3 has an IC₅₀of 7.4,19.7,16.9,no effect,76.8,and 5.3μM for the above cells;The IC₅₀of the compound 4 of above cells was 16.3,4.4,5.7,5.5,7.9and 5.0μM;and the activity of compound 5 was still under screening.Third:32 compounds each more than 5 mg in the natural product pool of the research group were selected,cells including MCF-7,MDA-MB-231,Hela,Hep-3B,A549,Huh-7,Hela/VCR,Hela/DDP,A549/Taxol were screened for antitumor activity,and the results showed that some of the compounds had good antitumor activity against the above cells.Fourth:32 natural products with more than 5 mg were selected from the natural product pool,and the anti-diabetic activity was measured by zebrafish.The results showed that more than half of the compounds promoted the value-added effect on isletβcells in different degrees.The effect of compound 25 on isletβcell proliferation is comparable to that of positive drugs.In summary,two Fujian coastal fungi were used as the target strains for large-scale fermentation,and 9 compounds were obtained,of which 5 were new compounds and 4were known compounds.Compound 1-4 had strong cellular antitumor activity.Anti-tumor and anti-diabetes screening was performed on the compounds in the natural product pool of the research group,and some compounds had strong anti-tumor and anti-diabetic activities.