Synthesis and evaluation of 17alpha-(carboranylalkyl)estradiols as ligands for estrogen receptors alpha and beta
Abstract
A series of 17a-(carboranylalkyl)estradiols was synthesized using cross-metathesis reaction of 17a-allyland 17a-vinylestradiols with allylcarboranes catalyzed by Hoveyda-Grubbs 2nd generation catalyst. The prepared estradiol derivatives were tested in the panel of cell-based reporter assays including all steroid receptors.
The compounds mainly activated estrogen receptors a and b and tended to be weakly selective for ERa. Besides ERa and ERb, we have also detected a weak agonistic activity on AR and PR at micromolar concentrations.
We didn't observe any antagonistic effect with the exception of two receptors: GR and MR which were inhibited with some of the tested ligands. However, the inhibition was detectable at concentrations exceeding by far those needed to activate estrogen receptors.