Design and synthesis of novel bicalutamide and enzalutamide derivatives as antiproliferative agents for the treatment of prostate cancer

• DOI: 10.1016/j.ejmech.2016.04.052
• Publication Date: 2016-04-29T07:00:49Z
• Authors: Marcella Bassetto; Salvatore Ferla; Fabrizio Pertusati; Sahar Kandil; Andrew D. Westwell; Andrea Brancale; Christopher McGuigan
• Keywords: Enzalutamide; Bicalutamide

Prostate cancer (PC) is one of the major causes male death worldwide and development new more potent anti-PC compounds a constant requirement. Among current treatments, (R)-bicalutamide enzalutamide are non-steroidal androgen receptor antagonist drugs approved also in case castration-resistant forms. Both these present moderate antiproliferative activity their use limited due to resistant mutants biological target. Insertion fluorinated perfluorinated groups biologically active trend medicinal chemistry, applied improve efficacy stability profiles. As means obtain such effects, different modifications with perfluoro were rationally designed on bicalutamide structures, leading synthesis series compounds. Several analogues displayed improved vitro towards four prostate cell lines, while maintaining full AR antagonism therefore representing promising leads for further development. Furthermore, molecular modelling studies performed conformation, providing useful insights potential protein-ligand interactions.