Scalarane sesterterpenes from a marine sponge of the genus Spongia and their FXR antagonistic activity.
Three new scalarane-based sesterterpenes, 1- 3, were isolated from a marine sponge of the genus Spongia, and their chemical structures were elucidated by analysis of HRMS and 2-D NMR spectra. The isolated compounds 1 and 3 showed inhibition against the farnesoid X-activated receptor (FXR) with IC50 values of 2.4 and 24 microM, respectively. In particular, compound 3 directly inhibited the interaction between FXR and a coactivator peptide (SRC-1) as determined by surface plasmon resonance (SPR) spectroscopy.
Nam
Sang-Jip
SJ
Center for Marine Natural Products and Drug Discovery, School of Earth and Environmental Sciences, Seoul National University, NS-80, Seoul, 151-747, Korea.
Ko
Hyunsil
H
Ju
Moon Kyeong
MK
Hwang
Hoosang
H
Chin
Jungwook
J
Ham
Jungyeob
J
Lee
Byoungchan
B
Lee
Jaehwan
J
Won
Dong Hwan
DH
Choi
Hyukjae
H
Ko
Jaeyoung
J
Shin
Kyoungjin
K
Oh
Taekyung
T
Kim
Seokho
S
Rho
Jung-Rae
JR
Kang
Heonjoong
H
D000818:Animals; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors*; D054830:Sesterterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D000099150:Receptor, Farnesoid X-Activated
D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D054830:Sesterterpenes; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated