Speaker
Description
Multiple tumors have been proven to be hormone-dependent, meaning that their development and growth are induced by endogenous human hormones. This fact was the basis for the design and development of antitumor steroidal drugs such as testolactone and exemestane. With the same goal in mind, we have performed a synthesis of C19-halogenated steroidal D-homo lactones. Previously synthesized 5α-bromo-6β-hydroxy D-homo lactone derivative1 was used as a starting compound. It was transformed into a 19-hydroxy derivative through two synthetic steps: 6,19-epoxidation and reductive epoxide opening. Next synthetic steps led to the synthesis of two new halogenated derivatives as well as one intermediate and two side products. All novel synthesized compounds, halogenated, intermediate, and side products, were tested in silico for their ADME properties (SwissADME Prediction), and in vitro for their cytotoxicity against a panel of cancer cell lines (MTT). Their relative binding affinities to the ligand-binding domains of androgen receptor and estrogen receptor α and β isoforms, were measured using a fluorescence-based assay in yeast.
Keywords: androstane, cytotoxicity, hormone derivatives
