Synthesis of novel galeterone derivatives and evaluation of their in vitro activity against prostate cancer cell lines
Language English Country France Media print-electronic
Document type Journal Article
PubMed
31271960
DOI
10.1016/j.ejmech.2019.06.040
PII: S0223-5234(19)30566-5
Knihovny.cz E-resources
- Keywords
- Galeterone, Prostate, Steroid,
- MeSH
- Androstadienes chemical synthesis chemistry pharmacology MeSH
- Benzimidazoles chemical synthesis chemistry pharmacology MeSH
- Cell Line MeSH
- PC-3 Cells MeSH
- Humans MeSH
- Molecular Structure MeSH
- Prostatic Neoplasms drug therapy metabolism pathology MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents chemical synthesis chemistry pharmacology MeSH
- Drug Screening Assays, Antitumor MeSH
- Cell Survival drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 3-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene MeSH Browser
- Androstadienes MeSH
- Benzimidazoles MeSH
- Antineoplastic Agents MeSH
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.
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