The Secondary Metabolites Chemical Ecological Role And Pharmacological Activity Of Four Sarcophyton Sp. Derived Epiphytic Fungi From The Soft Coral Of The South China Sea

The coral reef ecosystem is the largest ecosystem in the tropical ocean, a widerange and a huge number of marine life make full use of limited resources for survivalin the coral reef ecosystems, and the marine ecology have a high pressure, high salt,hypoxia, protected from light and other special environmental characteristics, whichmake the fierce competition between the various marine organisms such as fightingfor biological food and space. Soft corals and many other marine invertebrates havesoft, fleshy and fragile tissues without physical defense capability against theirpotential predators. However, they can survive in the competitive environmentsbecause of their chemical defensive system. In the last few years, many new chemicaldefensive compounds such as antifeeding, antifouling, allelopathy and anti-microbialwere obtained from soft coral, and some of them have shown potentials to beexploited as marine drugs. It is noted that the chemical defense compounds in the softcoral is not only important chemical and ecological significance, and somecompounds also showed potent pharmacological activity. Therefore, to explore therelationship between the chemical ecology activity and pharmacological activity, havea certain enlightening to find new marine drugs. The microorganisms isolated frommarine ivertebrates may be involved in the biosynthesis of active chemical ecologycompounds in the host, such as sea anemone toxins, conotoxins. Consequently,according to comparison the secondary metabolites to research the relationshipbetween microorganisms and the host, and to explore the effect of the microorganismsin the host chemical defense has become the excitement of marine chemical ecology.In this study,15epiphytic fungi was isolated from the soft coral Sarcophyton sp.(GX-WZ-20080011), which was collected from the South China Sea, under theguidance of the chemical defense activity model, four epiphytic fungi includingAlternaria sp., Aspergillus elegans, Aspergillus versicolor and Lophiostoma sp. wereselect for fermentation. The secondary metabolites were isolated by column chromatography on silica gel, Sephadex LH-20and preparative HPLC, and identifiedby spectroscopy of NMR, MS, IR, UV, X-ray, CD and chemical methods. From theseorganisms,79compounds (1–79) were respectively determined, including18newcompounds. More than8structural types were found, including24anthraquinones,5benzoquinones,20nitrogen compounds,5terpenoids,7steroids,11aromaticcompounds, and2lipids.20derivatives of anthraquinones (10a–b,12a–g,20a–c,21a–c,24a–b) have been prepared by acetylation, methylation, propionyl, benzyl forfurther research on structure and activity relationships.The chemical ecology effects including antifouling activity against the larvaesettlement of barnacle, growth-inhibition of microalgae and toxicity against zebrafishwere used to find active compounds.13compound were found to have ecologicalactivity, such as benzoquinones25shows strong anti-barnacle adhesion activity, withEC50value of0.27μg/mL.Pharmacological activity were also evluated and to explorethe structure-activity relationship.Compounds10,12and39were found to have not only significance in chemicalecology but also various pharmacological activities. Such as compound10displayed48h tail teratogenicity of zebrafish at the concentrate of2.4μg/mL,72h death ofzebrafish at the concentrate of2.91μg/mL; and potent growth-inhibition activitytowards microalgae with EC50of1.16μg/mL. In addition to the chemical ecologyactivity, this compound showed strong cytotoxicity toward five tumor cells, ashepatoma cells (HepG2and Hep3B), breast cancer adriamycin-resistant cells(MCF-7/ADR) and prostate cancer (PC-3) and colon cancer cells (HT-116), with theIC50values of0.70–2.85μg/mL, and the IC50value of HCT-116to0.70μg/mL isclose to the positive control drug epirubicin to0.48μg/mL. The structure and activityrelationships of these compound were discussed.In this study, under the guidance of the chemical ecological models, a variety ofstructural types of bioactive natural products were isolated from four softcoral-derived epiphytic fungi, and the anthraquinones which had potent activity wereprepared to to obtain series of derivatives.The absolute configuration of the hydrogenated anthraquinones were determinedby chemical methods. The relationship between chemical ecology activity andpharmacological activity of the active compounds was preliminary discussed. It is thefirst time to investigate the the role of microorganisms in the chemical defense ofthe soft coral Sarcophyton sp. All these results provide basis for finding the lead compounds of marine drugs, the further studies on chemical ecology and exploring forfinding new medicinal bioresources.