Secondary Metabolites From Three Codium Fragile-Endophytic Fungi And Their Bioactivities

Marine microorganisms possess highly diverse metabolism pathways. Among them, theresearch on the secondary metabolites of marine endophytic and epiphytic fungi has drawnthe interest of more and more natural product chemists. In this dissertation, three Codiumfragile endophytic fungi strains including Gibberella zeae, Aspergillus ustus, A.versicolor,were selected as aimed strains to be fermented for further investigation of secondarymetabolites. Most of the isolated compounds were preliminary screened on their bioactivities.The compounds were isolated from the fermentation extracts by repeated columnchromatography (CC) on silica gel and Sephadex LH-20, as well as by preparative thin layerchromatography (pTLC), preparative HPLC and recrystallization. The structures of thesecompounds were elucidated by means of spectroscopic methods including IR, UV, EI-MS,HR-EI-MS,1D-NMR (~1H-NMR,~13C-NMR, DEPT) and2D-NMR (1H-1HCOSY, HSQC,HMBC, NOESY). Totally,35compounds were structurally elucidated. From the extracts ofGibberella zeae,9compounds were isolated and structurally elucidated, including one newindoloditerpenes (GZ1) and eight steroids compounds (GZ2-GZ9). From the extracts offungus A. ustus,9steroids were isolated and structurally elucidated. Among them, one newsteroid compound (AU1) was found. From the extracts of fungus A. versicolor,17compoundswere also isolated and structurally elucidated, including one new sesquiterpenoid (AV1), onesterigmatocystin (AV2), five indoloditerpenes (AV3-AV7), one asperamide (AV8) and ninesteroids (AV9-AV17).The antibacterial actitity results show that indoloditerpenes compounds GZ1(AV3)、AV4、AV5and AV6, sesquiterpenoid AV1, steroids AU1、AU3、AU4(AV17)、AV9、AV10and AV16, sterigmatocystin AV2showed weak inhibitory activity againstStaphylococcus aureus. Compound AU1、 AU3、 AU9、 AV1、 AV9、 AV10amdAV11exhibited weak inhibitory activity against Escherichia coli.The results of toxicity against brine shrimp show that steroids GZ2-GZ9, AU1-AU9,AV9-AV17exhibited moderate or weak activities against brine shrimp. Compound GZ7(AU5,AV14) showed potent activities to toxicities against brine shrimp. Compounds AV9、AV1、AV8and AV2also exhibited potent activities to toxicities against brine shrimp, the IC50ofthem were14.85μg/mL、34.99μg/mL、27.71μg/mL and0.29μg/mL, respectively. The results of acetylcholinesterase (AChE) inhibitory activity showed that allcompounds possessed low activity to modulate AChE.Compound GZ1was evaluated for its cytotoxic activities. The results showed that itpossessed61.8%and17.6%inhibitory rates against A-549and BEL-7402tumor cell lines at10μM, respectively. No significant activity was detected against HL-60tumor cell lines.In this dissertation, secondary metabolites of three strains of marine endophytic fungiwere thoroughly studied. It enriched the chemical structures of marine natural products.Through bioassay, some compounds were found to be active. It may be helpful to explorationof marine microorganisms.