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.
- MeSH
- androstadieny chemická syntéza chemie farmakologie MeSH
- benzimidazoly chemická syntéza chemie farmakologie MeSH
- buněčné linie MeSH
- buňky PC-3 MeSH
- lidé MeSH
- molekulární struktura MeSH
- nádory prostaty farmakoterapie metabolismus patologie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- exemestan,
- MeSH
- anastrozol MeSH
- androstadieny chemie MeSH
- aromatasa * fyziologie chemie MeSH
- inhibitory aromatasy * farmakologie chemie MeSH
- letrozol MeSH
- lidé MeSH
- nádory prsu farmakoterapie MeSH
- nitrily chemie MeSH
- protinádorové látky farmakologie chemie MeSH
- triazoly chemie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
