Bioactive Polyoxygenated Steroids From The Beihai Gorgonian Menella Kanisa

The South China Sea is a rich resource of invertebrates possessing structurally uniquesecondary metabolites with various bioactivities such as antitumor, anti-virus, antibiosis, anti-inflammatory, anti-allergy, and immunomodulation bioactivities. As part of ongoing research on chemical constituents and bioactivities of marine organisms, we collected one of species of gorgonian Menella kanisa from Guangxi Beihai of the South China Sea for discovering new bioactive compounds or leading compounds.The gorgonian Menella kanisa was subjected to repeated colomn chromatographies including normal-phase silica gel, Sephadex LH20, and RP-HPLC, to give fourteen new steroids (6,9,14-18,20-23,25-27) having carbon skeletons of cholestane, ergostane, and24-norcholestane, together with thirteen known analogues (1-5,8,10-13,19,24,28-33). The structures of the compounds were elucidated by detailed analysis of spectroscopic data and comparison with reported data, These structures were reported for the first time from the title gorgonian. Compounds12and13were reported for the first time from natural sources.In the bioassay in vitro, these compounds exhibited different levels of growth inhibition activity against A549and MG-63cell lines, The compounds of9、11、24and27have a good inhibitory effect on A549and MG-63cells, ICsoin11.0-15.2and12.2～20.1μM. Structure-activity relationship study showed that, the nature of side chain may play an important role in the activity, and the same skeleton t with a greater polarity side chain has a weaker activity. A substitution of a5-hydroxy or an oxidation of6-hydroxy to a ketone group may decrease the activity whereas the contribution of the1-ketone group remains uncertain.Compounds28-33were submitted to in vitro anti-microbial activity bioassay towards Microbotryum violaceum, Botrytiscinerea, Septoria tritici, Escherichia coli and Bacillus megaterium. The active of28,29,33to Microbotryum violaceum than the positive control of penicillin and streptomycin, showed significant inhibitory activity; The active of29,31-33to Botrytiscinerea than the positive control of penicillin and streptomycin, showed significant inhibitory activity; The active of29-31,33to Septoria tritici than the positive control of streptomycin, showed significant inhibitory activity; The active of29,30to Escherichia coli than the positive control of streptomycin, showed significant inhibitory activity; The active of29-31to Bacillus megaterium than the positive control of streptomycin and ketoconazole, showed significant inhibitory activity.Aimed to explore the marine resources, studying the bio-active constituents and finally look for the prodrug from marine natural products, our group has been inverstigating the chemical constituents from Chinese marine invertebrates systematically. As part of our ongoing program of searching for biologically active substances from corals, this research was the first time to study the chemical constituents from gorgonian Menella kanisa, and obtained a series of sterols.