Chemical Investigations Of Four Endophytic Fungi And One Plant With Their Biological Activities

Endophytic fungi are microorganisms which have a certain stage or the whole stage of life inside the healthy host tissues or organs without causing any disease symptoms.In the process of co-evolution with the host,endophytic fungi produce a variety of metabolites with novel structures and significant biological activities,which have been warmly concerned by natural product chemists.As a rich reservoir of genetic diversity,endophytic fungi provide sustainable,novel and bioactive lead products for people as an important sources.However,for some special species such as bryophytes and lichens,chemical investigations of their endophytic fungi have a great significance.In this paper.four endophytic fungi(including one endophytic fungus of a liverwort and three endolichenic fungi)and a medicinal plant Fructus swietenia macrophylla were subjected to chemical investigation.On the basis of pre-screening activity,Aspergillus fumigatus.Phialocephala fortinii,Phaeosphaeria avenaria f.sp.and Ulospora bilgramii were selected for amplified fermentation in rice culture medium.The fermentation products extracted by ethyl acetate and Fructus swietenia macrophylla extracted by methanol were followlly fractioned using column chromatography on silica gel.sephadex LH-20,ODS,as well as reversed-phase high performance liquid chromatography(RP HPLC).A total of 78 compounds,32 of them were news,were obtained from the four endophytic fungi and one plant.The structures of these compounds were determined by mass spectrometry(MS),nuclear magnetic resonance(NMR)techniques,X-ray diffraction analysis with Cu K? radiation and circular dichroism(CD)analysis,etc.These products were evaluated for their cytotoxicity activity,inhibitory activity against the fungus Candida albicans and inhibitory activity of a-glucosidase.Some of them revealed strong activites.Compounds 25 and 30 exhibited potent activity for the reversal of azole resistance by combination with fluconazole(FLC).Further analysis showed that compounds 25 and 30 specifically modulate the expression of MDR1 to inhibit the activity of drug efflux pumps and therefore reverse azole resistance.