title: Tuberatolides, potent FXR antagonists from the Korean marine tunicate Botryllus tuberatus.
abstract: One isoprenoid, tuberatolide A (1), meroterpenoids tuberatolide B (2) and 2'-epi-tuberatolide B (3), and the known meroterpenoids yezoquinolide (4), (R)-sargachromenol (5), and (S)-sargachromenol (6) were isolated from the Korean marine tunicate Botryllus tuberatus. The structures of these compounds were elucidated by NMR, MS, and CD spectroscopic analyses. These terpenoids antagonized the chenodeoxycholic acid (CDCA)-activated human farnesoid X receptor (hFXR) in a cell-based co-transfection assay with IC(50) values as low as 1.5 μM without significant effect on steroid receptors. Furthermore, they released the co-activator peptide from the CDCA-bound hFXR ligand binding domain in cell-free surface plasmon resonance experiments.
authors.affiliation: Center for Marine Natural Products and Drug Discovery, School of Earth and Environmental Sciences, Seoul National University, NS-80, 151-747, Seoul, Korea.
authors.forename: Hyukjae
authors.initials: H
authors.lastname: Choi
authors.forename: Hoosang
authors.initials: H
authors.lastname: Hwang
authors.forename: Jungwook
authors.initials: J
authors.lastname: Chin
authors.forename: Euno
authors.initials: E
authors.lastname: Kim
authors.forename: Jaehwan
authors.initials: J
authors.lastname: Lee
authors.forename: Sang-Jip
authors.initials: SJ
authors.lastname: Nam
authors.forename: Byoung Chan
authors.initials: BC
authors.lastname: Lee
authors.forename: Boon Jo
authors.initials: BJ
authors.lastname: Rho
authors.forename: Heonjoong
authors.initials: H
authors.lastname: Kang
mesh_terms: D000818:Animals; D006801:Humans; D007723:Korea; D008386:Marine Biology; D019906:Nuclear Magnetic Resonance, Biomolecular; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors*; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014561:Urochordata / Q000737:chemistry*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D013729:Terpenes; D000099150:Receptor, Farnesoid X-Activated; C557963:tuberatolide A