Structural Changes of 6a-Hydroxy-Pterocarpans Upon Heating Modulate Their Estrogenicity

Abstract

The isoflavonoid composition of an ethanolic extract of fungus-treated soybean sprouts was strongly altered by a combined acid/heat treatment. UHPLC-MS analysis showed that 6a-hydroxy-pterocarpans were completely converted to their respective, more stable, 6a,11a-pterocarpenes, whereas other isoflavonoids, from the isoflavone and coumestan subclasses, were affected to a much lesser extent (loss of ∼15%). Subsequently, mixtures enriched in prenylated 6a-hydroxy-pterocarpans (pools of glyceollin I/II/III and glyceollin IV/VI) or prenylated 6a,11a-pterocarpenes (pools of dehydroglyceollin I/II/III and dehydroglyceollin IV/VI) were purified, and tested for activity on both human estrogen receptors (ERα and ERβ). In particular, the response toward ERα changed, from agonistic for glyceollins to antagonistic for dehydroglyceollins. Toward ERβ a decrease in agonistic activity was observed. These results indicate that the introduction of a double bond with the concomitant loss of a hydroxyl group in 6a-hydroxy-pterocarpans extensively modulates their estrogenic activity.

Involvement of a Hydrophobic Pocket and Helix 11 in Determining the Modes of Action of Prenylated Flavonoids and Isoflavonoids in the Human Estrogen Receptor

“…Determination of estrogenic activity : In vitro estrogenic activity was determined by means of a yeast‐based bioassay as described elsewhere with slight modifications. Dilution series of each sample were prepared in DMSO, ranging from 1×10 −11 to 1×10 −4 m instead of 0.0001 to 10 μg mL −1 (≈3×10 −10 to 3×10 −5 m ).…”

“…Dilution series of each sample were prepared in DMSO, ranging from 1×10 −11 to 1×10 −4 m instead of 0.0001 to 10 μg mL −1 (≈3×10 −10 to 3×10 −5 m ). EC 50 values and antagonistic activities were determined as described earlier . If EC 50 values could not be determined, due to poor solubility or toxicity, as sometimes observed at high concentrations, agonistic activity was indicated with an EC 50 greater than the highest concentration measured.…”

“…EC 50 values and antagonistic activities were determined as described earlier. [36] If EC 50 values could not be determined, due to poor solubility or toxicity,a ss ometimes observed at high concentrations, agonistic activity was indicated with an EC 50 greater than the highest concentration measured. The relative estrogen potency (REP) of ac ompound was determined by dividing the EC 50 of E 2 by the EC 50 of the compound.…”

Phytochemicals Targeting Estrogen Receptors: Beneficial Rather Than Adverse Effects?

“…Their structure is described as a benzo-pyrano-furano-benzene, where the B-rings are coupled to position 4-one [ 34 ]. Glyceollins, which correspond to prenylated 6a-hydroxy pterocarpans, are the main delegates of this family [ 35 ]. They belong to phytoalexin and are produced from daidzein via an enzymatic pathway, mainly in soybean, by the action of a diversity of elicitors such as UV stress, bacterial or fungi infection [ 36 ].…”

Structural basis for non-genuine phenolic acceptor substrate specificity of Streptomyces roseochromogenes prenyltransferase CloQ from the ABBA/PT-barrel superfamily

“…The only substrates that were A-ring prenylated were equol and genistein, albeit the latter in minute amounts. It was not possible to annotate the ring position of the prenyl group in coumestrol, as coumestrol does not undergo typical RDA fragmentation [30, 31]. Consequently no apparent A- or B-ring fragment ions were formed in MS n .…”