New Bioactive Compounds From The Starfish Certonardoa Semiregularis

Starfish is known to yield a large number of unique bioactive metabolites such as steroids. These steroids have been reported to exhibit cytotoxic, hemolytic, antiviral, antifungal, and antimicrobial activities. In our search for bioactive metabolites from the starfish Certonardoa semiregularis (family Linckiidae), collected from Korean waters, thirty-two steroids, and two taurine derivatives have been isolated from the brine shrimp active fraction of the MeOH extract.The gross structures of the compounds were elucidated as fourteen new polyhydroxysterols (1-5, 7-12, 14-16), two known polyhydroxysterols (6, 13), fourteen new glycosides of polyhydiroxysteroids (17-21, 23-30, 32), two known glycosides of polyhydroxysteroids (22, 31), a new taurine derivative (34), and a known taurine derivative (33). The gross structures of the compounds were determined on the basis of COSY, HMQC (or HSQC), and HMBC experiments, while the geometries of the double bonds were assigned by the 1H-1H coupling constants or 13C NMR data. The absolute configuration was defined on the basis of spectral analysis and chemical manipulation.Compounds 2, 4, 5, 7-9,11,14,16,18, 24, 25, 27, 28, 30, and 32 lack the 8-hydroxy group, which is the distinctive feature of most polyhydroxysteroids so far isolated from starfish. The side chains of 10 and 11 were first encountered in naturally occurring sterols. Compounds 17-21 contain previously undescribed2-O-methyl-B-D-xylopyranosyl-(1 2)-3-O-sulfonato-B-D-xylopyranosyl unit as a sugar moiety. The sugar moiety 2,4-di-0-methyl-B-D-xylopyranosyl-(1 2)-B-D-xylofuranosyl unit in compounds 23-28 was also unprecedented. The nonsubstituted xylofuranosyl unit incompound 32 has not been encountered in the starfish saponins.Compounds 1-11, and 14-32 were further tested for cytotoxicity against five human solid cancer cell lines [human lung cancer (A549), human ovarian cancer (SK-OV-3), human skin cancer (SK-MEL-2), human CNS cancer (XF498), human colon cancer (HCT15)]. Compounds 1-11, 14, 16, 27, and 32 showed moderate to significant cytotoxicity against all of the five human cancer cell lines. Compound 19 displayed potent cytotoxicity against the SK-MEL-2 skin cancer. Compounds 17, 25, 26, 28, and 31 showed somewhat selective cytotoxicity against the SK-MEL-2 skin cancer.Certain sterols of similar structure to compounds 1-11 were reported to show antimicrobial activity. Therefore, compounds 1-11, along with compounds 26-28 and 32 were assayed for antibacterial activity against 20 clinically isolated strains. Most of these compounds displayed only weak antibacterial activity against Streptococcus pyogenes 308A, Pseudomonas aeruginosa 1771, and Pseudomonas aeruginosa 1771M.Some sulfated compounds and compounds 17a, 22, and 25 were evaluated for antiviral activity since certain sulfated sterols from marine invertebrate were reported to be active. It was reported that sterols sulfated exclusively on the A and B rings were much more potent than other sulfated sterols. However, the antiviral activity of these compounds was insignificant within the range of non-cytotoxic concentration. Only weak antiviral activity against HSV was observed in compounds 17a, 29, and 30. Compounds 17 and 19 rather exhibited cytotoxicity against the MT-4 cell.