Investigating the anti-oestrogenic effect of p-Synephrine and de novo design of oestrogen receptor modulating molecules

Abstract

p-synephrine is the active ingredient in Citrus aurantium which is a major component of weight loss preparations. A uterotrophic assay carried out by Arbo et al. on immature female mice demonstrated that p-synephrine could act as an antagonist at the oestrogen receptor. This warrants consideration because these formulations are used indiscriminately by young women. 17βoestradiol has a high affinity for the oestrogen receptor; consequently it was used as a benchmark against which the affinity of p-synephrine and the de novo designed non-steroidal molecules could be compared. Binding affinities of the psynephrine molecules were relatively low (pKd= 4.5-5.0) compared to that of 17β-oestradiol (pKd 7.23). However, the de novo generated molecules had affinities ranging between 5.6-8.48. This gives a good indication that these molecules could potentiallydisplace 17β-oestradiol from the oestrogen receptor ligand binding pocket and that they could be further developed for the treatment of breast cancer and osteoporosis.