Synthesis and Structure–Activity Relationships of Novel Non-Steroidal CYP17A1 Inhibitors as Potential Prostate Cancer Agents

Tomasz M. Wróbel*, Oksana Rogova, Katyayani Sharma, Maria Natalia Rojas Velazquez, Amit V. Pandey, Flemming Steen Jørgensen, Frederic S. Arendrup, Kasper L. Andersen, Fredrik Björkling

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

7 Citations (Scopus)
24 Downloads (Pure)

Abstract

Twenty new compounds, targeting CYP17A1, were synthesized, based on our previous work on a benzimidazole scaffold, and their biological activity evaluated. Inhibition of CYP17A1 is an important modality in the treatment of prostate cancer, which remains the most abundant cancer type in men. The biological assessment included CYP17A1 hydroxylase and lyase inhibition, CYP3A4 and P450 oxidoreductase (POR) inhibition, as well as antiproliferative activity in PC3 prostate cancer cells. The most potent compounds were selected for further analyses including in silico modeling. This combined effort resulted in a compound (comp 2, IC50 1.2 µM, in CYP17A1) with a potency comparable to abiraterone and selectivity towards the other targets tested. In addition, the data provided an understanding of the structure–activity relationship of this novel non-steroidal compound class.

Original languageEnglish
Article number165
JournalBiomolecules
Volume12
Issue number2
ISSN2218-273X
DOIs
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • CYP17A1
  • Cytochrome P450 17A1
  • Enzyme inhibition
  • Prostate cancer

Cite this