2. Academic Validation
  3. Synthesis of novel galeterone derivatives and evaluation of their in vitro activity against prostate cancer cell lines

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

  • Eur J Med Chem. 2019 Oct 1:179:483-492. doi: 10.1016/j.ejmech.2019.06.040.
Radek Jorda 1,  Eva Řezníčková 2,  Urszula Kiełczewska 3,  Jadwiga Maj 3,  Jacek W Morzycki 3,  Leszek Siergiejczyk 3,  Václav Bazgier 4,  Karel Berka 5,  Lucie Rárová 2,  Agnieszka Wojtkielewicz 6
Affiliations

Affiliations

  • 1 Laboratory of Growth Regulators, The Czech Academy of Sciences, Institute of Experimental Botany & Palacký University, Šlechtitelů 27, 783 71, Olomouc, Czech Republic. Electronic address: radek.jorda@upol.cz.
  • 2 Laboratory of Growth Regulators, The Czech Academy of Sciences, Institute of Experimental Botany & Palacký University, Šlechtitelů 27, 783 71, Olomouc, Czech Republic.
  • 3 Institute of Chemistry, University of Białystok, K. Ciołkowskiego 1K, 15-245, Białystok, Poland.
  • 4 Department of Chemical Biology and Genetics, Centre of the Region Haná for Biotechnological and Agricultural Research, Palacky University & Institute of Experimental Botany ASCR, Šlechtitelů 27, 78371, Olomouc, Czech Republic; Department of Physical Chemistry, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacky University, 17. listopadu 12, 771 46, Olomouc, Czech Republic.
  • 5 Department of Physical Chemistry, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacky University, 17. listopadu 12, 771 46, Olomouc, Czech Republic.
  • 6 Institute of Chemistry, University of Białystok, K. Ciołkowskiego 1K, 15-245, Białystok, Poland. Electronic address: a.wojtkielewicz@uwb.edu.pl.
PMID: 31271960 DOI: 10.1016/j.ejmech.2019.06.040
Abstract

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.

Keywords

Galeterone; Prostate; Steroid.

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