Synthesis, characterization, and estrogen receptor binding affinity of flavone-, indole-, and furan-estradiol conjugates

Different flavone-, indole-, and furan-17β-estradiol conjugates, linked via alkyl spacer chains extending from the 17α-position of the estradiol moiety, were synthesized by Pd-catalyzed cross-coupling reactions. Structures were assigned based on spectroscopic data. In vitro competitive binding assays for the estrogen receptor (α-ER), using [3H]estradiol (RBA = 100) as a competitor, revealed that a two-carbon alkyl linker combined with a flavone conjugate provided the highest binding affinity (RBA ∼ 9), warranting further studies on their potential use as selective estrogen-receptor modulators (SERMs) for hormone-replacement therapies.

Graphical abstractFlavone-, indole-, and furan-17β-estradiol conjugates with 2–8 carbon linker chains extending from the 17α-position of the estradiol were synthesized by Pd-catalyzed cross-coupling reactions. In vitro competitive binding assays for the estrogen receptor revealed that a two-carbon alkynyl linker combined with a flavone conjugate provided the highest binding affinity.Figure optionsDownload full-size imageDownload as PowerPoint slide