Structure–Activity Relationship of Phytoestrogen Analogs as ERα/β Agonists with Neuroprotective Activities

Hye Won Cho, Hyo Jin Gim, Hua Li, Lalita Subedi, Sun Yeou Kim, Jae-Ha Ryu, Raok Jeon
2021 Chemical and pharmaceutical bulletin  
A set of isoflavononid and flavonoid analogs was prepared and evaluated for estrogen receptor α (ERα) and ERβ transactivation and anti-neuroinflammatory activities. Structure-activity relationship (SAR) study of naturally occurring phytoestrogens, their metabolites, and related isoflavone analogs revealed the importance of the C-ring of isoflavonoids for ER activity and selectivity. Docking study suggested putative binding modes of daidzein 2 and dehydroequol 8 in the active site of ERα and
more » ... site of ERα and ERβ, and provided an understanding of the promising activity and selectivity of dehydroequol 8. Among the tested compounds, equol 7 and dehydroequol 8 were the most potent ERα/β agonists with ERβ selectivity and neuroprotective activity. This study provides knowledge on the SAR of isoflavonoids for further development of potent and selective ER agonists with neuroprotective potential.
doi:10.1248/cpb.c20-00706 pmid:33390527 fatcat:rbv6cg3bpbehlpuyhdgmvl2nl4