The Secondary Metabolites And Bioactivities Of Several Medicinal Bioresources From Typical Tropic Marine Environment In China

Coral reefs and mangrove wetlands are two typical tropic marine environment. Invertebrates from coral reef ecosystem and plants from mangrove ecosystem, rich in novel bioactive secondary metabolites, have become the most important bioresources for screening and discovery of lead compounds and marine drugs. In the processes of searching for new medicinal marine bioresources and bioactive natural products, several tropic marine species have been chemically investigated, including five species of marine invertebrates from the coral reefs and two species of mangrove plants from the tropic wetlands in the coastal area.Five invertebrates in cluding soft corals Sinularia compacta, Sarcophyton crassocaule, Sarcophyton infundibuliforme, gorgonian Menella sp. and sponge LCJ-1 (unidentified), and two mangrove plants Bruguiera sexangula and Cerbera manghas were collected from the tropic coral reefs and wetlands from the South China Sea. The secondary metabolites were isolated by column chromatography on silica gel, Sephadex LH-20 and preparative reversed phase HPLC, and identified by spectroscopy of NMR, MS, IR, UV, CD and X-ray, as well as chemical processes. From these organisms, 116 compounds were obtained, including 19 new compounds and 1 metabolite isolated from natural source for the first time. More than 14 structural types were found, including 27 diterpenoids, 15 sesquiterpenoids, 10 triterpenoids, 18 steroids, 13 lipids, 7 flavonoids, 2 iridoids, 2 cyclic polysulfides, 2 quinone derivatives, 1 lignanoid, 1 coumarin, 2 carotinoids, 10 alkaloids and 6 aromatic compounds.Soft corals S. compacta and S. infundibuliforme were chemically studied for the first time. Seven diterpenes that belong to four biogenetically related diterpenoid structural classes were isolated from S. compacta, which may provide foundation for investigation of their biogenetic pathway. It is the first report to isolate spatane-type diterpenes from soft coral source, which were only found in brown algae previously. Two glycoglycerylethers consisting of lyxose residue and chimyl alcohol moiety isolated from Sarcophyton infundibuliforme are the first example of co-occurrence of both C-2 epimers of naturally occuring glycosylglycerol derivatives.The bioactivities of the compounds were evaluated by high-throughput screening programs on various of screening modles including anticancer, antiinflammatory, antidiabetes, enzyme inhibition and immunosuppression. A variety of bioactive compounds have been found, including 23 cytotoxic compounds, 4 antiinflammatory compounds, 5 antidiabetes compounds, 3 enzyme inhibition compounds, 2 voltage-gated potassium current inhibition compounds and 4 immunosuppression compounds. Cardiac glycoside 99 exhibited significant cytotoxicity against A-549 cell line, with an IC50 value of 0.496±0.034μg/ml. The structure-function relationship analysis suggested that the increase ofβ-D-Glucose group at C-4 of digitoxose of cardiac glycosides resulted in the rapid descend of cytotoxicity. The acetylation of the hydroxy group at C-2 of digitoxose significantly contributed to cytotoxicity. While the configuration of C-17 at aglycone, the configuration of C-2 at digitoxose as well as the epoxy at 7/8 at aglycone exhibited minor impact to cytotoxicity. Triterpenoid 70 exhibited significant cytotoxicity against A-549 cell line, with an IC50 value of 37.068±1.610 ng/ml. Diterpenoid 1 show strong inhibition toward DPPⅣ, with an IC50 value of 0.190±0.010μg/ml. Aromatic lactone 106 showed inhibition activity against pancreatic lipase with an IC50 value of 4.73μM. These bioactive compounds demonstrated high values for further exploitation for lead compounds and even for new drug discovery.The secondary metabolites of invertebrates from coral reef ecosystem and plants from mangrove ecosystem were compared and analyzed. It indicated that terpenoids, steroids, lipoids and aromatic compounds are common constituents in these organisms, in spite of the different skeletons. Constituents of quinone terpenoids, carotenoids and nitrogenous compounds were found from the coral reef invertebrates, while flavonoids, lignanoids, coumarins and iridoids were isolated form the wetland mangroves. Polar compounds with high water-solubility, such as indole derivaives, basyl, nucleosides, internal salt, quaternary amine and glycosylglycerol derivatives were derived form the invertebrates, whereas volatile compounds such as cyclic polysulfides and benzene derivatives derived from the mangroves.Many enlightenments should be gain from the investigation of structures and functions of the secondary metabolites from the different typical marine environments. The bioactive marine secondary metabolites from coral reef ecosystem and mangrove ecosystem provided diversity of compounds for the discovery of lead compounds and exploration of new medicinal bioresources.