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

Pertusati, Fabrizio ORCID: https://orcid.org/0000-0003-4532-9101, Ferla, Salvatore ORCID: https://orcid.org/0000-0002-5918-9237, Bassetto, Marcella ORCID: https://orcid.org/0000-0002-2491-5868, Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419, Kandil, Sahar ORCID: https://orcid.org/0000-0003-1806-9623, Westwell, Andrew D. ORCID: https://orcid.org/0000-0002-5166-9236 and McGuigan, Christopher 2019. A new series of bicalutamide, enzalutamide and enobosarm derivatives carrying pentafluorosulfanyl (SF5) and pentafluoroethyl (C2F5) substituents: Improved antiproliferative agents against prostate cancer. European Journal of Medicinal Chemistry 180 , pp. 1-14. 10.1016/j.ejmech.2019.07.001

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Publisher:	Elsevier
ISSN:	0223-5234
Date of First Compliant Deposit:	7 August 2019
Date of Acceptance:	1 July 2019
Last Modified:	12 Nov 2024 00:45
URI:	https://orca.cardiff.ac.uk/id/eprint/124785

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