Globostelletins A-I, cytotoxic isomalabaricane derivatives from the marine sponge Rhabdastrella globostellata.
Nine new isomalabaricane-derived natural products, globostelletins A-I (1-9), were isolated from the marine sponge Rhabdastrella globostellata, together with jaspolides F (10), rhabdastrellic acid-A (11), (-)-stellettin E (12), stellettins C (13) and D (14). The structures of these compounds were determined on the basis of extensive spectroscopic analyses and by comparison with the reported data in the literature. The inhibitory activities of compounds 1-12 against human tumor cell lines were evaluated, and their structure-activity relationships were discussed. In addition, rhabdastrellic acid-A (11) showed potent inhibition against HL-60 cells, and it induced the apoptosis of HL-60 cells in M/G2 phase. The mechanism of 11 targeting the ubiquitin-proteasome system, including the regulation of ChT-L and T-L target proteins is discussed.
Li
Jin
J
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, People's Republic of China.
Xu
Bo
B
Cui
Jinrong
J
Deng
Zhiwei
Z
de Voogd
Nicole J
NJ
Proksch
Peter
P
Lin
Wenhan
W
D000818:Animals; D017209:Apoptosis; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D011161:Porifera / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity
D014315:Triterpenes; C529429:rhabdastrellic acid A