Synthesis of novel galeterone derivatives and evaluation of their in vitro activity against prostate cancer cell lines

0509260 - ÚEB 2020 RIV FR eng J - Journal Article
Jorda, Radek - Řezníčková, Eva - Kiełczewska, U. - Maj, J. - Morzycki, J.W. - Siergiejczyk, L. - Bazgier, Václav - Berka, K. - Rárová, Lucie - Wojtkielewicz, A.
Synthesis of novel galeterone derivatives and evaluation of their in vitro activity against prostate cancer cell lines.
European Journal of Medicinal Chemistry. Roč. 179, OCT 1 (2019), s. 483-492. ISSN 0223-5234. E-ISSN 1768-3254
R&D Projects: GA ČR(CZ) GA19-01383S; GA MŠMT(CZ) LM2015047
Institutional support: RVO:61389030
Keywords : Galeterone * Prostate * Steroid
OECD category: Organic chemistry
Impact factor: 5.573, year: 2019
Method of publishing: Open access
http://dx.doi.org/10.1016/j.ejmech.2019.06.040

Prostate cancer is one of the main causes of male cancer-related deaths worldwide and the suppression of androgen receptor signalling is established as an effective strategy for the treatment. A series of galeterone analogues including several steroid-fused azacycles, as well as 17-(benzimidazol-1-ylimino), 16α-(benzimidazol-2-ylamino), and 16α-(benzothiazol-2-ylamino) steroid derivatives, were synthesized and tested against prostate cancer cell lines. Candidate compound 3f was shown to reduce AR-regulated transcription in a dose-dependent manner in nanomolar ranges and suppress expression of AR-regulated proteins Nkx3.1 and PSA in 22Rv1-ARE14 and VCaP cancer cell lines. Flexible docking study revealed similar position of 3f within AR binding site in comparison of galeterone even with stronger binding energy.
Permanent Link: http://hdl.handle.net/11104/0300005