Synthesis, characterization and binding affinities of rhenium(I) thiosemicarbazone complexes for the estrogen receptor (α/β)

The binding affinities towards estrogen receptors (ERs) α and β of a set of thiosemicarbazone ligands (HLn) and their rhenium(I) carbonyl complexes [ReX(HLn)(CO)3] (X = Cl, Br) were determined by a competitive standard radiometric assay with [3H]-estradiol. The ability of the coordinated thiosemicarbazone ligands to undergo deprotonation and the lability of the ReX bond were used as a synthetic strategy to obtain [Re(hpy)(Ln)(CO)3] (hpy = 3- or 4-hydroxypyridine). The inclusion of the additional hpy ligand endows the new thiosemicarbazonate complexes with an improved affinity towards the estrogen receptors and, consequently, the values of the inhibition constant (Ki) could be determined for some of them. In general, the values of Ki for both ER subtypes suggest an appreciable selectivity towards ERα.

Graphical abstractThe binding affinity towards estrogen receptors α and β of several thiosemicarbazone ligands (HLn) and their complexes [ReX(HLn)(CO)3] was determined. These complexes can be transformed in the hydroxypyridine derivatives [Re(hpy)(Ln)(CO)3]. The affinity of these thiosemicarbazonato complexes is substantially improved and the values of Ki suggest selectivity towards the ERα.Figure optionsDownload full-size imageDownload as PowerPoint slide