Chemical Constituents And Bioactivities Of The Marine Sponge Diacarnus Megaspinorhabdosa From Paracel Islands

The South China Sea is a rich resource of invertebrates possessing structurally unique secondary metabolites with various properies such as antivirus, antitumor, anti-inflammatory, antimalarial, antimicrobial and immunomodulation bioactivities, which become the important source of drug leads for the scientists. Marine natural products have been the focus of chemistry research for a long time. According to the statistics, metabolites reported from the marine sponge accounted for about one third of all the marine natural products every year.The marine sponge Diacarnus megaspinorhabdosa belonging to order Hadromerida, family Latrunculiidae and genus Diacarnus, it distributed abundantly in the South China Sea. Sponges of genus Diacarnus are recognized as being prolific sources to produce terpene peroxides and related derivatives, which include norterpene ketones, dienes, diols and other types of compounds. Recently, attention has been drawn on these metabolites because of their pharmaceutical properties, including antimalarial, antimicrobial, Trypanosoma brucei inhibitory, sea urchin egg cell-division inhibitory, cytotoxic, antiulcer and antihypotensive activities. In order to discover new antimalarial compounds or leads compounds from marine sponges inhabited in the South China Sea, we investigated the chemical constituents and bioactivities of the marine sponge D. megaspinorhabdosa from the Paracel Islands of the South China Sea.In this study, chemical investgated of the sponge D. megaspinorhabdosa led to the isolation and determination of 30 metabolites from the CH2Cl2 extract guided by using 1H-NMR and 13C NMR screening, solvent extraction and chromatographic methods including VLC, LPLC, MPLC, HPLC on silica gel, ODS C-18 and Sephadex LH-20 were used. Among these compounds, including 16 norterpene peroxides,6 norterpene ketones,2 steroids, and 6 other types of compounds, which were elucidated b 1H-NMR,13C-NMR, HMQC (HSQC),1H-1H COSY, HMBC, NOESY, MS and CD. They were determined as: aikupikoxides C-D (1-2), aikupikoxide A (3), (-)-ent-muqubilone methyl ester (4), (S)-metyl-2-((3S,6S)-6-((E)-4,8-dimethyl-nona-3,7-dienyl)-6-methyl-1,2-dioxan-3-yl) propanoate (5), sigmosceptrellin E nethyl ester (6), diacarperoxides M (7), diacarperoxides N (8), diacarperoxide H (9), epimuqubilin B (10), muqubilin (11), muqubilin methyl ester (12), nuapapuin A methyl ester (13), diacarperoxide A (14), diacarperoxide I(15), diacarperoxide J (16), diacarlactones A-F (17-22), muquketone (23), phthalic acid isodibutyl ester (24), bis(2-ethylhexyl)benzene-1,2-dicarboxylate (25), methyl trans-9-hexadecenoate (26),11-Hexadecenoic acid-15-methyl-methyl ester (27), methyl (cis-5,8,11,14,17)-eicosapenta enoate (28), cholesterol (29), cholestan-3-ol (30). Compounds 7-8,17-22 are new compounds. Compounds 26-30 are reported for the first time in the genus Diacarnus.Their antimalarial, cytotoxicity, protein tyrosine phosphatase 1B and antimicrobial activities have been evaluated. The results showed that compound 17 exhibited moderate cytotoxicity against cancer cell lines NCI-H446, NCI-H440, SGC-7901, HeLa and MCF-7 with IC50 values of 18.5,20.1,22.3,26.7 and 47.1 μM, respectively. The other tested compounds were not cytotoxic (IC50> 50μM) toward the five cancer cell lines. Diacarperoxides H, I, and J (9,15,16) showed antimalarial activity against Plasmodium falciparum (W2 clones) in vitro with IC50 values of 12.9,4.8 and 1.8 μM, while 15 and 16 exhibited antimalarial activity in vitro against P. falciparum (D6 clones) with IC50 values of 7.9 and 1.6 μM, respectively.The study focused on the chemical constituents of D. megaspinorhabdosa and their bioactivities from D. megaspinorhabdosa collected from Paracel Islands of South China Sea by using 1H NMR and 13C NMR guided separation. Multiple methods have been used to determine the absolute configurations of the new structures. A plausible biogenetic pathway for these compounds was proposed. The results of bioactivity test indicate that some compounds exhibited potential antimalarial and cytotoxicity activities, which could provide new leads for the development of new antimalarial drugs and also improve the knowledge of structurally diverse of metabolites from the genus of sponge Diacarnus.