Alkaloids From A Gorgonian-Derived Fungus And Their Bioactivities

Invertebrates such as corals and sponges together with microorganisms are mainsources for marine natural products. Especially, in recent years corals has become oneof the research hotspots. Although corals lack of essential physical defensive strategy,they can survive in the complex environment depending on the production ofdefensive metabolites. These chemical defensive compounds may also be thepharmacological active secondary metabolites. But it was reported thatmicroorganisms were the real production of the bioactive products, which have beenthought to be produced by the corals. A literature search revealed that about100compounds were reported from coral-derived fungi, including new compounds andmetoblites isolated from the source for the first time. Metabolites from coral-derivedfungi mainly contain terpenoids, alkaloids and quinones, and they usually possesspotent antibacterial, cytotoxic, antifouling activities. Herein, we report the research onthe secondary metabolites especially alkaloids from a gorgonian-derived fungusisolated from the South China Sea and their bioactivities.The fungus Scopulariopsis sp., isolated from a gorgonian coral Carijoa sp.(GX-WZ-2010001) collected from Weizhou coral reef in2010, was selected becausethe EtOAc extracts of both its fermentation broth and mycelia exhibited strongantibacterial activity. Moreover, literature survey revealed that there were limitedreports on the metabolites of the genus Scopulariopsis sp. Secondary metabolites ofScopulariopsis sp. derived from gorgonian corals remain unknown until now. Sixteenpure compounds were isolated from the crude extracts by use of columnchromatography on silica gel, Sephadex LH-20and preparative HPLC. And11compounds were identified as fumiquinazoline L (1), scopuquinolones A–D (2–4,7),aflaquinolones A (5), D (6), F (8), G (9), cyclopenin (10), sterigmatocystin (11) on thebasis of1D and2D NMR, MS, IR, UV, CD and X-Ray diffraction. Compounds1–4 and7are new compounds. All the compounds were isolated from the species for thefirst time.Compound1was an alkaloid with a heptacyclic skeleton formed via a bridginghemiaminal linkage, named as fumiquinazoline L. The structure and absoluteconfiguration were identified by comprehensive spectroscopic data and X-raydiffraction analysis. During acid hydrolysis of1, the isomerization of the valineresidue was observed and also studied in different conditions. Moreover, the chiralcenters of C-3, C-14and C-17in two related analogues fumiquinazolines C and Hwere also discussed. The biosynthesis pathway of fumiquinazoline L (1) fromanthranilate, Trp and Ala was proposed. Compounds2–9were series ofdihydroquinolin-2-one containing alkaloids, and their structures were determined byNMR and CD spectra, compounds2,5and7were further confirmed by X-raydiffraction analysis. The biosynthesis of quinuoline compounds2–9from anthranilicacid, methionine and phenylalanine were also presumed.Fumiquinazoline L (1), compounds4and5showed weak cytotoxic towardshuman lung cancer cell line A549with IC50of18.4,29.6and30.0μM, respectively.Compound4exhibited selective strong antibacterial activity against V.parahaemolyticus and V. anguillarum with the MIC values of1.56μM for each,which was equivalent to or stronger than that of ciprofloxacin used as the positivecontrol. Compound7showed extensive antibacterial activity against the testedbacteria, especially S. aureus, B. cereus, V. parahaemolyticus, V. anguillarum, P.putida with the MIC values of0.78,1.56,6.25,0.78and1.56μM, respectively. Itshould be noted that the obvious difference in the antibacterial activities ofcompounds7,8and9, indicating that the methoxyl at position3played apparent rolein antibacterial activity, while the stereochemistry of position C-3and C-4did notappreciably change the MIC values. Compounds1,6,7,8and11showed stronglethalities toward brine shrimp Artemia salina with LC50values of2.22,1.16,0.79,7.85and0.56μM, respectively.In this dissertation, secondary metabolites from a gorgonian-derived fungus fromthe South China Sea were isolated and their structures were identified. The biosynthesis of the isolated alkaloids were discussed. Their bioactivities of cytotoxicactivity towards tumour cells, antibacterial activity and lethality toward the brineshrimp A. salina were evaluated, and the structure-activity relationships were analysed.The above work provides a material foundation for the research on marine naturalproducts.