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 H-1, C-13, DEPT, HMQC, and HMBC NMR experiments. The most potent estrogenic activity of these isolated natural products in an estrogen receptor (ER alpha) competitive-binding assay was for 3, which exhibited an IC50 value of 80 mu M, compared with 18 nM for the natural steroid 17 beta-estradiol. Results were interpreted via virtual docking of isolated compounds to an ER alpha crystal structure.