Guttiferone I, a new prenylated benzophenone from Garcinia humilis as a liver X receptor ligand.
Liver X receptors (LXR) have been implicated in cholesterol homeostasis. Agonists of LXR are expected to increase cholesterol efflux, lower LDL, and raise HDL levels. Screening of a natural product library of plant extracts using a LXR-SPA binding assay and bioassay-guided fractionation of the bark and stem extract of Garcinia humilis led to the discovery of a new polyisoprenylated benzophenone named guttiferone I (1). The IC(50) value for this compound in the LXRalpha-SPA binding assay was 3.4 muM. Details of the isolation, structure elucidation, and ligand binding activity of 1 are described.
Herath
Kithsiri
K
Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA.
Jayasuriya
Hiranthi
H
Ondeyka
John G
JG
Guan
Ziqiang
Z
Borris
Robert P
RP
Stijfhoorn
Eirik
E
Stevenson
Dennis
D
Wang
Jianhua
J
Sharma
Neelam
N
Macnaul
Karen
K
Menke
John G
JG
Ali
Aisha
A
Schulman
Marvin J
MJ
Singh
Sheo B
SB
D001577:Benzophenones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029760:Garcinia / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008024:Ligands; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors; D015394:Molecular Structure; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
D001577:Benzophenones; D004268:DNA-Binding Proteins; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C501151:guttiferone I