3β,5α,6β-Oxygenated sterols from the South China Sea gorgonian Muriceopsis flavida and their tumor cell growth inhibitory activity and apoptosis-inducing function

Three new polyhydroxysterols, named muriflasteroids A–C (1–3) were isolated from the South China Sea gorgonian Muriceopsis flavida, together with sixteen known analogs, cholest-3β,5α,6β-triol,3β-acetate (4), 5α-methoxycholest-3β,6β-diol (5), (22E)-cholest-22-en-3β,5α,6β-triol (6), cholest-3β,5α,6β-triol (7), (22E)-24-norcholest-22-en-3β,5α,6β-triol (8), (22E,24S)-ergost-22-en-3β,5α,6β-triol (9), ergost-24(28)-en-3β,5α,6β-triol (10), (22E)-cholest-7,22-dien-3β,5α,6β-triol (11), cholest-7-en-3β,5α,6β-triol (12), (22E)-24-norcholest-7,22-dien-3β,5α,6β-triol (13), ergost-7,24(28)-dien-3β,5α,6β-triol (14), (22E,24R)-ergost-7,22-dien-3β,5α,6β-triol (15), (22E)-cholest-22-en-1β,3β,5α,6β-tetrol (16), (22E)-24-norcholest-22-en-1β,3β,5α,6β-tetrol (17), cholest-1β,3β,5α,6β-tetrol (18), and (24ξ)-ergost-1β,3β,5α,6β-tetrol (19). The structures of the new compounds were elucidated by detailed spectroscopic analysis in combination with comparison of reported data. All the compounds are reported for the first time from the animal. In the bioassay in vitro, these compounds exhibited different levels of growth inhibition activity against A549 and MG63 cell lines. In particular, compound 18 displayed a considerable activity, being similar as that of positive control adriamycin. An annexin V analysis indicated that compounds 7 and 18 can significantly induce apoptosis in A549 cell, and compound 7 is more potent in the induction of apoptosis. Preliminary structure–activity analysis suggests that the acetylation on 3-OH and appearance of Δ7 may decrease the activity while substitution of 1-OH and the nature of side chain may also play an important role in the activity. Methylation of 5-OH contributed a little to the activity.

Figure optionsDownload as PowerPoint slideHighlights
► Nineteen 3β,5α,6β-oxygenated sterols were identified from Muriceopsis flavida.
► The structures were reported for the first time from the title gorgonian.
► The steroids exhibited growth inhibition activity against A549 and MG63 cells.
► Compounds 7 and 18 can significantly induce apoptosis in A549 cells.
► A preliminary attempt was made for the structure–activity relationship study.