Study On Chemical Constituents And Antibacterial And Antitumor Activities Of Ethyl Acetate Layer Of Tubeufia Rubra PF02-2

Fungi are a big group of organisms that are widely distributed in nature.The fungus is widely recognized for its ability to produce clinical medicines.There are about 1.5 million fungi,but only 5%of them are known species,and the proportion of known fungi that have been studied for chemical composition and biological activity is even lower.Therefore,it is very scientifically meaningful to conduct in-depth research on fungi.Our research group previously isolated and obtained a saprophytic fungus,Tubeufia rubra PF02-2,from rotting trees in freshwater streams in Fangchenggang City,Guangxi Province.The results of previous studies have shown that the fermented crude extract of this fungus has antitumor and multidrug resistance reversal activities.This dissertation mainly researches antibacterial,antitumor,and multidrug resistance reversal.We isolated and identified 16 compounds（1–16）from this fungus.Including one nitrogen-containing glyceride（Rubracin A）,one eight-membered cyclic ether carboxylate methyl ester,four nucleosides,one L-alanine,one acetophenone,one pyranoside,one benzoate,one benzaldehyde,two formanilides,one ergosterol,and two steroidal glycosides.Nitrogen-containing glycerides and eight-membered cyclic ether carboxylate were identified as new compounds by nuclear magnetic resonance,high-resolution mass spectrometry,and circular dichroism spectroscopy,and the rest were known compounds.All compounds were preliminarily evaluated for their antibacterial activity,antitumor activity,and multidrug resistance reversal activity.It was found that all compounds had no antibacterial activity against five pathogenic bacteria and one pathogenic fungus.Compounds 10,15,and 16 have significant inhibitory activity against human non-small cell lung cancer cells（A549）,human malignant embryonic rhabdoid cells（RD）,and human tongue squamous cell carcinoma cells（Tca）,and their half-inhibitory concentrations(IC₅₀)are respectively 43.925,34.172,and 37.539μg/m L;16.905,51.954,and 29.553μg/m L;and 50.069,38.382,and 49.453μg/m L;The tumor reversal activity assay found that the IC₅₀ of doxorubicin against three drug-resistant cell lines（MCF-7/Adr,A549/Adr,and K562/Adr）was significantly reduced when 20μg/m L of Rubracin A and doxorubicin were combined.Compared with those without Rubracin A,the reductions were 42.2%,27.2%,and 25.5%,respectively.The detection of the key protein of multidrug resistance（P-glycoprotein）showed that the P-glycoprotein content of Rubracin A combined with doxorubicin treatment was significantly lower than that of the doxorubicin-treated group.It is speculated that Rubracin A may reverse the multidrug resistance of tumor cells by down-regulating the expression of P-glycoprotein（P-gp）.Through the study of the chemical constituents and biological activities of Tubeufia rubra,this thesis confirmed the potential of Tubeufiaceae to produce anti-tumor and multidrug-resistant active compounds.It provides clues and a theoretical basis for the rational development and utilization of Tubeufiaceae fungi.