Synthesis, in vitro steroid receptor binding and in silico testing of novel 17α-(pyridin-2-yl)estra-1,3,5(10),16-tetraen derivatives

Steroid compounds incessantly attract attention due to their biological and clinical importance. Considering that many cancers are hormone-dependent, synthetically modified steroid molecules are suitable candidates for the treatment of these malignancies. It has been established that steroid compounds with a heterocyclic ring or heteroatoms in their structure represent potential anticancer agents, and also have other important pharmacological properties. With this in mind, we have synthesized novel 17-(pyridin-2-yl)estra-1,3,5(10),16-tetraen compounds, starting from 17β-hydoxy-17α-(pyridin-2-yl)-estra-1,3,5(10)-triene derivatives by dehydratation reactions. For all synthesized compounds we analyzed in silico ADMET properties using the online SwissADME tool and ProTox II virtual lab. Since these modified compounds are based on steroidal scaffolds, their relative binding affinities for the ligand-binding domains of estrogen receptor α and β and androgen receptor were evaluated using a fluorescent assay in yeast.