Estrogenic Activity of Chemical Constituents from Tephrosia candida

In a continued investigation of medicinal plants from the genus Tephrosia, phytochemical analysis of a methylene chloride–methanol (1:1) extract of the air-dried aerial parts of Tephrosia candida afforded two new 8-prenylated flavonoids, namely, tephrocandidins A (1) and B (2), a new prenylated chalcone, candidachalcone (3), a new sesquiterpene (4), and a previously reported pea flavonoid phytoalexin, pisatin (5). The structures of 1–4 were established by spectroscopic methods, including HREIMS, and ¹H, ¹³C, 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 3, which exhibited an IC₅₀ 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.