Chemistry And Bioactivity Investigation On Secondary Metabolites From Two Plant Pathogenic Fungi

Humans are facing a threate by nearly 25,000 to 30,000 kinds of diseases including cancer,however merely a small part of these disease can be cured.In order to speed up the discovery of drug lead compounds,the researchers turned their attention to special eco-environment fungi.special eco-environment-derived fungi were stimulated by specific environmental factors that may produce new secondary metabolites pathways and new metabolites.These new metabolites often with good bioactivity and thus have potential treatment effect.In this study,plant pathogenic fungi from special eco-environment were screened through the high performance liquid chromatography(HPLC)fingerprints analysis and the bioactivity screening.As a result,two strains of Leptosphaeria sp.GB10 and Coniochaeta cephalothecoides F821 were put into further chemical investigation.One new alkaloid(1),one known alkaloid(2),two unsaturated fatty acid derivatives(3-4),and one cerebroside(5)were isolated from the culture of Leptosphaeria sp.Two new alkaloids(6-7),three known alkaloids(8-10),one tryptophan derivative(12)and two phenolic acids(11,13)were isolated from the culture of Coniochaeta cephalothecoides.A total of 13 secondary metabolites were isolated,3 of them were new ones;the structures of the new natural products were elucidated by nuclear magnetic resonance(NMR)and mass spectrometry(MS)techniques.These isolated compounds were evaluated for their cytotoxicity against several human tumor cell lines and nitric oxide inhibitory activity.The results show that compounds 1?2?8?9?10 have moderate cytotoxicity against threee cell lines A549?K562 and H460,respectively.Compounds 3 and 4 shows inhibition against nitric oxide production in macrophages with 77.60% and 80.94% at the concentration of 25.0 ?M,respectively.Compound 5 presented nitric oxide inhibitory activity with IC50 value of 80?M.Results from chemical studies of the selected two strains of plant pathogenic fungi have afforded a variety of new bioactive metabolites.These preliminary results implied that the plant pathogenic fungi,especially the unique and chemically under-explored plant pathogenic fungal species could be another important source of bioactive natural products,and warrant further chemical investigations to explore their metabolic potential.