title: 3β,5α,6β-Oxygenated sterols from the South China Sea gorgonian Muriceopsis flavida and their tumor cell growth inhibitory activity and apoptosis-inducing function.
abstract: 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.
authors.affiliation: Research Center for Marine Drugs, and Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo-He Road, Shanghai 200433, PR China.
authors.forename: Tao-Fang
authors.initials: TF
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Zhang
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Liu
authors.forename: Zeng-Lei
authors.initials: ZL
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Yao-Cheng
authors.initials: YC
authors.lastname: Rui
authors.forename: Tie-Jun
authors.initials: TJ
authors.lastname: Li
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002681:China; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009792:Oceans and Seas; D052616:Solid Phase Extraction; D013261:Sterols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D013261:Sterols; C581587:muriflasteroid A; C581588:muriflasteroid B; C581589:muriflasteroid C