Studies On The Chemical Constitutents And Their Bioactivities Of Sinularia Sp.

The genus Sinularia is a sessile animal of the Family Alcyoniidae, Suborder Alcyoniina, Order Alcyonacea, Subclass Octocorallia, Class Anthozoa, Phylum Cnidaria, widely distributed in the seas of the world. Literature search confirmed that42species of the genus Sinularia have been sudied, and many terpenoids, steroids and a few rare polyketides have been discovered. The South China Sea contains plentiful of marine organisms, notably soft coral. In our ongoing program to search for natural products with unique structural features and pronounced biological activities, we have performed a systematica investigation on the chemical constituents and biological activities of the Sinularia sp. collected from the coast of Weizhou, the south of China, in July,2007.Isolation and structure determination: Monitoring by bioassay-guided isolation, the MeOH extract of the Sinularia sp. was chromatographed on silica gel, TLC and Sephadex LH-20, and semi-preparative HPLC, respectively. Then twenty-seven compounds were isolated and purified from the Sinularia sp., among wich twenty-two compounds were identified on the basis of spectral methods (IR、 NMR、MS、CD and caculated ECD etc.) and their physicochemical properties. What is remarkable is that seven new compounds (1～7) were obtained, including of four polyketides with a novel skeleton, sinularone A (1)、sinularone B (2)、sinularone C (3) and sinularone E (4); a rare spirocyclic sesquiterpene, sinularone D (5), and two sterols, sinularol A (6) and sinularol B (7); The other known compounds were identified as gorgosterol (8), cholesterol (9)、(22E)-ergosta-5,22-dien-3β-ol (10)、cholesta-5,20-dien-3β-ol (11),ergosta-5,24(28)-dien-3β-ol (12),(22E)-3β-hydroxycholesta-5,22-dien-7-one (13)、3β-hydroxyergosta-5,24(28)-dien-7-one (14),(222s)-3β-hydroxyergosta-5,22-dien-7-one (15),3β-hydroxyergosta-5-en-7-one (16),3β-hydroxycholesta-5-en-7-one (17)、(22E)-5a-cholesta-7,22-diene-3β,5a,6β-triol (18)、24-methyl-5a-ergosta-3β,5a,6β-triol (19); and one enol,4,7,10-trien-1-ol (20); and two glycerol ethers, batyl alcohol (21)、3-(icosyloxy) propane-1,2-diol (22).Biological activities:Most pure compounds were evaluated for their cytotoxicities against P388(murine leukemia cell), HeLa (human cervical carcinoma cells) and K562(chronic myelogenous leukemia cell lines of the original) cancer cell lines by the MTT method. The results indicated that compounds18had moderate cytotoxicities against Hela and K562at10μg/mL. And most pure compounds were evaluated for the inhibition rate against tyrosine kinase c-Met by the enzyme-linked immunosorbent assay (ELISA) method at the molecular level. The results indicated that compounds2had moderate inhibition for the c-Met at10μg/mL.Moreover, possible biosynthetic pathways of polyketides with a novel skeleton (1-4) were postulated according to their structures and literatures in the paper.