2. Academic Validation
  3. A new series of bicalutamide, enzalutamide and enobosarm derivatives carrying pentafluorosulfanyl (SF5) and pentafluoroethyl (C2F5) substituents: Improved antiproliferative agents against prostate cancer

A new series of bicalutamide, enzalutamide and enobosarm derivatives carrying pentafluorosulfanyl (SF5) and pentafluoroethyl (C2F5) substituents: Improved antiproliferative agents against prostate cancer

  • Eur J Med Chem. 2019 Oct 15:180:1-14. doi: 10.1016/j.ejmech.2019.07.001.
Fabrizio Pertusati 1,  Salvatore Ferla 2,  Marcella Bassetto 2,  Andrea Brancale 2,  Sahar Khandil 2,  Andrew D Westwell 2,  Christopher McGuigan 2
Affiliations

Affiliations

  • 1 School of Pharmacy and Pharmaceutical Sciences, Redwood Building, King Edwards VII Avenue, CF10 3NB, Cardiff, Wales, UK. Electronic address: pertusatif1@cardiff.ac.uk.
  • 2 School of Pharmacy and Pharmaceutical Sciences, Redwood Building, King Edwards VII Avenue, CF10 3NB, Cardiff, Wales, UK.
PMID: 31288149 DOI: 10.1016/j.ejmech.2019.07.001
Abstract

SAR studies on bicalutamide, enobosarm and enzalutamide analogues, functionalised with polyfluorinated groups, is presented. Among the novel bicalutamide and enobosarm derivatives synthesised, several displayed significantly improved in vitro Anticancer activity, with IC50 values in the low micromolar range against four different prostate Cancer cell lines (LNCaP, VCaP, DU-145 and 22Rv1), showing up to 48-fold increase in comparison with the parent structures. In particular, SF5 enobosarm analogues were found to be most potent compounds, full AR antagonists and with favourable ADME properties. The most promising compound (48a) was evaluated for its in vivo efficacy in PC xenograft mouse model (22Rv1) with results comparable to the standard-of-care docetaxel.

Keywords

Androgen receptor; Antiproliferative activity; Bicalutamide; Enobosarm; Enzalutamide; Pentafluoroethyl; Pentafluorosulfanyl; Prostate cancer.

Figures