a
Laboratory of Food Chemistry, Wageningen University, P.O. Box 17, Wageningen, Netherlands
b Wageningen NMR Centre, Wageningen University, Wageningen,
b Wageningen NMR Centre, Wageningen University, Wageningen,
Abstract
Seven prenylated
6a-hydroxy-pterocapans and five prenylated 6a,11a-pterocarpenes with
different kinds of prenylation were purified from an ethanolic extract
of fungus-treated soybean sprouts. The activity of these compounds
toward both human estrogen receptors (hERα and hERβ) was determined in a
yeast bioassay and the activity toward hERα was additionally tested in
an U2-OS based hERα CALUX bioassay. In the yeast bioassay, compounds
with chain prenylation showed in general an agonistic mode of action
toward hERα, whereas furan and pyran prenylation led to an antagonistic
mode of action. Five of these antagonistic compounds had an agonistic
mode of action in the U2-OS based hERα CALUX bioassay, implying that
these compounds can act as SERMs. The yeast bioassay also identified 8
ER subtype-selective compounds, with either an antagonistic mode of
action or no response toward hERα and an agonistic mode of action toward
hERβ. The ER subtype-selective compounds were characterized by
6a-hydroxy-pterocarpan or 6a,11a-pterocarpene backbone structure. It is
suggested that either the extra D-ring or the increase in length to
12-13.5 Å of these compounds is responsible for an agonistic mode of
action toward hERβ and, thereby, inducing ER subtype-selective behavior.
© 2015 Elsevier Ltd. All rights reserved.
Author keywords
6a,11a-Pterocarpene; 6a-Hydroxy-pterocarpan; hER yeast bioassay; hERα-CALUX; Molar extinction coefficient; Prenylation
Indexed keywords
EMTREE drug terms: dehydroglyceollidin I;
dehydroglyceollidin II; dehydroglyceollidin III; dehydroglyceollidin IV;
estrogen receptor alpha; estrogen receptor beta; glyceofuran;
glyceollidin I; glyceollidin II; glyceollidin III; glyceollidin IV;
glyceollidin V; pterocarpan derivative; selective estrogen receptor
modulator; soybean extract; unclassified drug
EMTREE medical terms: Article; bioassay; computer
model; drug purification; drug structure; prenylation; soybean; ultra
performance liquid chromatography; yeast
