Study Of The Secondary Metabolites And Bioactivities Of Gorgonian S. Suberosa And The Gorgonian–derived Fungus A. Terreus

In this research, the secondary metabolites from a gorgonian Subergorgiasuberosa from the South China Sea and a fungus Aspergillus terreus derived from thegorgonian were isolated and identified. The biological activities of the isolatedcompounds were evaluated.Investigation on the gorgonian S. suberosa led to the isolation of eighteencompounds (1–18), including tweleve9,11-secosteriods (1–12), one sesquiterpenoids(13), two alkaloids (14–15) and three pregnant steroids (16–18). Among them,compounds1,2and4–6were new compounds.2/3and4/5were two pairs of C-24epimeric mixtures, and6/7was mixture of cis-trans isomers at Δ24(28). UPLC analysisof each of the mixtures revealed two closely linked chromatographic peaks, andfurther confirmed the presence of the epimers. The absolute configuration of thesteroidal nucleus was established by the modified Mosher’s method. Compounds11and12showed cytotoxic activity toward K562with the IC50values as6.22and5.10μM, respectively, suggesting that the length of the side chain may affect thecytotoxicity. To further study the effects of the three hydroxy groups in steroidalnucleus on cytotoxicity, five acetylated derivatives from12(12a12e) were preparedand evaluated for their cytotoxic activities. Among them,12b,12c and12d showedsignificant cytotoxicities against K562with the IC50values of1.09,3.79and2.49μM,respectively, which indicated that the acetylation of6-OH or/and11-OH group (12b,12c and12d) was helpful for the cytotoxicity. The cytotoxicity reduced significantlywhen3-OH was acetylated (12a and12e), suggesting that3-OH was important tocytotoxicity. Most of the isolated9,11-secosteriods also showed antiproliferativeeffects of embryonic condensatio on zebrafish Danio rario embryo and antifoulingactivities against the larvae of Balanus amphtrite. Investigation on the fungus A. terreus led to the isolation of nineteen compounds(19–37), including four Territrems (19–22), seven butyrolactones (23–29), onepeptide (30), three alkaloids (31–33), one lovastatin analogue (34), two steroids(35–36) and one terrain (37). Among them, compounds19and30were newcompounds, and the absolute confugation of compound30was determineded by theMarfey’s method. The Territrems and butyrolactones had potent antifouling activitiesagainst the larvae of Balanus amphtrite at nontoxic concentrations. The EC50valuesof compounds22and26were0.64and0.63μg/mL, respectively, and the LC50valueswere higher than50μg/mL. The results suggested that these classes of compoundshad potential for environment-friendly antifouling agent development.In conclusion,37compounds were isolated from a gorgonian from the SouthChina Sea and the fungus derived from the gorgonian. Among them, seven were newcompounds, and five were new9,11-secosteriods which enriched the structuraldiversity of the9,11-secosteriods. Diverse activity evaluation models were used tostudy the activities of the secondary metabolites, and the preliminarystructure-activity relationships were studied. This provides the basic information forlooking for pharmaceutical lead compounds from the ocean.