The Secondary Metabolites And Chmeical Ecologica Effects Of Four Corels And Two Symbitoic Fungic From South China Sea

The competitions between marine organisms which live in coral reef ecosystems are very common and cruel. Many invertebrates such as gorgonians, soft corals, have been suffered from a high pressure, high salt, and harsh environment of hypoxia for a long evolution period. Thus, some unique and diverse metabolic mechanisms have been built to adapt the competitive conditions during the evolutionary process. They can survive on their chemical defensive system including antifeedant, allelopathic and antifouling agents. Therefore, with the guidance of chemical ecological effects, searching for metabolites with chemical ecological activities could be a new important way to discover new marine drugs. In present paper, several tropical marine species, including four corals and two symbiotic fungi, have been chemically investigated to search for new bioactive compounds.Four corals including Pacifigorgia senta, Menella kanisa, Carijoa sp. and Scleronephthya gracillimum, and one gorgonian-derived fungus Talaromyces sp. and one sponge-derived fungus Nigrospora sp. have been chosen for chemical investigation. The secondary metabolites were isolated by column chromatography on si-gel, Sephadex LH-20 and pre-HPLC, and identified by spectroscopy methods of NMR, MS, IR and UV. From these organisms, 68 compounds （1–68） were obtained, including 11 new compounds. More than 9 structural types were found, including 4 sesquiterpenoids, 13 diterpenoids, 1 triterpenoids, 23 steroids, 12 aromatic compounds, 6 anthraquinone, 2 alkaloids, 1 cyclic ether and 6 lipids. Thirty-six derivatives of diphenyl ether （41-A–41-U;42-A–41-O） have been prepared by hydrolysis and transesterification reactions for further research on structure and activity relationships.Gorgonian P. senta, M. kanisa and soft coral S. gracillimum were chemically studied for the first time. From genus Pacifigorgia and Menella, 20 and 9 compounds have been isolated for the first time, respectively. Compound 34 was also found in genus Scleronephthya for the first time. The transformation pathway between diphenyl ether compounds was also discussed, and the radical reaction should be a possible approach that led to the transform from compound 44 to 46.The chemical ecology effects were evaluated with comprehensive bioassay methods, including lethal activity toward brine shrimp, antifouling activity against the larvae settlement of barnacle, growth-inhibition of microalgae and toxicity against zebrafish. A variety of active compounds have been found, including 14 compounds with lethality toward brine shrimp, 6 compounds with antifouling activitiy, 3 compounds with microalgae growth-inhibition activity and 9 compounds with zebrafish toxicity. Of all these active compounds, compounds 5 and 36 showed obviously lethality toward brine shrimp with 68% and 67 % mortality at a concentration of 10μg/mL. Compound 43 exhibited potent antifouling activity with IC₅₀ value of 2.25μg/mL, and showed toxicity to zebrafish after 72h with a IC₅₀ value of 1.25μg/mL. To complement the activity of chemical ecology, the metabolites were also evaluated for their pharmacological activities, such as cytotoxicity and anti-inflammation. Totally 14 compounds showed cytotoxicty toward tumor cell lines. Compound 49 exhibited strong activity against HepG2 with an IC₅₀ value of 2.86μg/mL. It shoud be pointed out that, compounds 34, 36, 41, 42 and 49 were found to have not only significance in chemical ecology but also various pharmacological activities. Compound 34 showed potent lethality with 54% mortality at a concentration of 25μg/mL, and moderate growth-inhibition activity towards microalgae with EC50 of 18.8μg/mL, as well as inhibition activity on the hatchability of zebrafish at the concentrate of 10μg/mL. In addition to the chemical ecology activity, this compound showed strong cytotoxicity toward HT-116 tumor cell line with the inhibition rate of 70.5% at the concentration of 10μmol/L. Compound 41 exhibited toxicity toward zebrafish, the hatchability was less than 10% at the same concentrate, and the EC50 for antifouling activity was 3.31μg/mL. Meanwhile, this compound showed potent toxicity toward HT-116 with the IC₅₀ value of 7.51μg/mL. In conclusion, in present study the allelopathic and antifouling activities of secondary metabolites from corals and symbiotic fungi have been evaluated under the guidance of chemical ecological models. Totally 19 compounds have been found to possess series of chemoecological activities. Furthermore, five compounds also showed potent cytotoxicity towards tumor cell lines. All these results provide basis for the further studies on chemical ecology and exploration for new medicinal bioresources.