Research On Anti-tumor And Anti-multidrug Resistance Activities Of Secondary Metabolites From Soft Coral Sinularia Sp.of South China Sea

There are 22,000 derived from the ocean among 153,000 natural products according to statistics,and more than 40 marine natural products among of them showed significant anti-tumor activity in clinical and pre-clinical studies.As so far,Yondelis(ET743)is the first one to treatment of the ovarian cancer.The succession of development of Yondelis inject new impetus for discovery of marine drug.Therefore,we research secondary metabolites from soft coral Sinularia sp.of South China Sea,the activities of anti-tumor and reversal activity to multi-resistance of cancer cell lines induced by Adriamycin,probe into the possible mechanisms of reversal activity to multi-resistance in order to further discovery the leading drug of antitumur.One novel nine-membered macrocyclic polysulfur cembranoid lactone sinulariaoid A(1),four new multioxygented cembranoids sinulariaoid B(2),sinulariaoid C(3),sinulariaoid D(4),sinulariaoid E(5)along with four known cembranoids dihydrosinularin(6),sinularin(7),dihydrosinuflexolide(8)and capilloloid(9)were isolated from the soft coral Sinularia sp,by all kinds of column chromatography,silica gel,Sephadex LH-20,ODS,and so on.Their structures were determined on the base of extensive spectroscopic methods,X-ray single-crystal diffraction analysis.Sinulariaoid A(1)was the first nine-membered macrocyclic polysulfur cembranoid from the soft coral.The cytotoxic activity of compounds 1?4 and 6?8 were tested on four human cancer cell lines(HepG2,HepG2/ADM,MCF-7 and MCF-7/ADR).Among these,sinularia A(1)has the most potent anticancer activity in vitro,and its cytotoxic effect against HepG2/ADM was more potent than that toward other three cell lines.Furthermore,it was found that sinularia A(1)induced apoptosis,and its selective toxicity towards HepG2/ADM cells is not related with P-glycoprotein.