Anti-oestrogenic diarylheptanoids from Aframomum melegueta with in silico oestrogen receptor alpha binding conformation similar to enterodiol and enterolactone

Aframomum melegueta is a spice widely used in African folk medicine. The chloroform soluble fraction of A. melegueta seeds yielded four new diarylheptanoids named gingerenone D (1), dihydrogingerenone A (2), dihydrogingerenone B(3), and dihydrogingerenone C (4), in addition to six known diarylheptanoids and hydroxyphenylalkanones. The most potent oestrogen receptor binding ability in an oestrogen receptor alpha (ER alpha) competitive-binding assay was for compounds 1, 2 and 5 with IC50 values of 50, 79 and 39 mu M, respectively, compared with 18 nM for the natural steroid 17 beta-oestradiol (E2). In addition, the diarylheptanoids 1, 2 and 5 showed anti-oestrogenic activity in a receptor cofactor assay system for ER alpha, while the hydroxyphenylalkanone, [6]dehydrogingerdione, (7) exhibited an agonistic action. Results were interpreted via virtual docking of the active compounds to an ER alpha crystal structure, in comparison with the known oestrogenic compounds: enterodiol (END), enterolactone (ENL), genistein and E2. The anti-oestrogenic compounds 1, 2 and 5 showed a binding similarity to that of END and ENL while compound 7 was similar in binding to genistein and E2 interpreting its agonistic effect. (C) 2012 Elsevier Ltd. All rights reserved.