Estrogenic Activity of Chemical Constituents from <i>Tephrosia candida</i>

In a continued investigation of medicinal plants from the genus <i>Tephrosia</i>, phytochemical analysis of a methylene chloride–methanol (1:1) extract of the air-dried aerial parts of <i>Tephrosia candida</i> afforded two new 8-prenylated flavonoids, namely, tephrocandidins A (<b>1</b>) and B (<b>2</b>), a new prenylated chalcone, candidachalcone (<b>3</b>), a new sesquiterpene (<b>4</b>), and a previously reported pea flavonoid phytoalexin, pisatin (<b>5</b>). The structures of <b>1</b>–<b>4</b> were established by spectroscopic methods, including HREIMS, and <sup>1</sup>H, <sup>13</sup>C, DEPT, HMQC, and HMBC NMR experiments. The most potent estrogenic activity of these isolated natural products in an estrogen receptor (ERα) competitive-binding assay was for <b>3</b>, which exhibited an IC<sub>50</sub> value of 80 μM, compared with 18 nM for the natural steroid 17β-estradiol. Results were interpreted via virtual docking of isolated compounds to an ERα crystal structure.