Studies On The Metabolites Of Two Wetland Sta Chybotrys Sp.fungi

Fungi are one of the most important resources of the clinical medicines.Due to the special living environment and unique defense system,special eco-environment microorganisms are more prone to producing secondary metabolites with unique structure and novel bioactivity.Therefore,special eco-environment microorganisms will become potential sources of novel natural agents for drug discovery.Two wetland fungi(DTH12-9 and PYH05-7)all belong to Stachybotrys sp.,which were collected from different wetland habitats(Poyang and Dongting lakes).The secondary metabolites were isolated and purified from the two fungi by a series of chromatography methods,such as ODS column chromatography,sephadex LH-20 column chromatography and reversed-phase high performance liquid chromatography(HPLC),etc.A total of 42 secondary metabolites were identified from the ethyl acetate crude extracts of two fungi,and 20 of them are new compounds belonging to different structural classes.The structures and configuations of all isolated compounds were elucidated by nuclear magnetic resonance(NMR)and mass spectrometry(MS)methods,in combination with X-ray diffraction analysis,chemical derivatizations(such as the modified Mosher's method,the circular dichroism(CD)analysis of the in situ formed Rh2(OCOCF3)4 complex),and the CD method.11(1-11)phenylspirodrimane skeleton compounds were obtained from the solid culture of Stachybotrys sp.(DTH12-9),including five new compounds(1-5).31(12-42)compounds were obtained from the solid culture of Stachybotrys Bisbyi(PYH05-7),and fifteen new compounds(12-26)belonging to different structural classes.Among them,compounds 12-15,are a new type of sesquiterpenoids and derived from the probotryane skeleton cleaved at C-4/C-5.This new type is named as seco-probotryane-type sesquiterpenoid.In addition,19-23 are the first glycosylation derivatives of botryane sesquiterpenoids.Furthermore,compounds 24 and 25 featured an undescribed seco-bisabosqual skeleton.Of the 11 compounds from Stachybotrys sp.(DTH12-9)screened for anti-HMG Co A reductase activities,compounds 2 and 7 resulted in a strong inhibition of yeast growth and also the addition of mevalonate exhibited a high rescuing effect.All of these result demonstrated that 2 and 7 have potential HMG-CoA reductase suppression activities.Primary analyses of the structure-activity relationships are discussed in this paper.In addition,parts of compounds against human cancer cell lines HL-60,SMMC-7721,A-549,MCF-7,and SW480 were evaluated by the MTT method,using cisplatin and paclitaxel as the positive controls.Compounds 1,4,9,and 42 showed moderate cytotoxic activities against five cellines.All isolated compounds were subjected to biological assays for antimicrobial activity against two bacterias(Staphylococcus aureus 209P and Escherichia coli ATCC0111)and two fungi(Candida albicans FIM709 and Aspergillus niger R330).However,compounds showed no activity.