Formation of 5α-dihydrotestosterone from 5α-androstane-3α,17ß-diol in prostate cancer LAPC-4 cells - Identifying inhibitors of non-classical pathways producing the most potent androgen.
Bioorg Med Chem Lett
; 30(2): 126783, 2020 01 15.
Article
em En
| MEDLINE
| ID: mdl-31753699
ABSTRACT
5α-Dihydrotestosterone (5α-DHT) possesses a great affinity for the androgen receptor (AR), and its binding to AR promotes the proliferation of prostate cancer (PC) cells in androgen-dependent PC. Primarily synthesized from testosterone (T) in testis, 5α-DHT could also be produced from 5α-androstane-3α,17ß-diol (3α-diol), an almost inactive androgen, following non-classical pathways. We reported the chemical synthesis of non-commercially available [4-14C]-3α-diol from [4-14C]-T, and the development of a biological assay to identify inhibitors of the 5α-DHT formation from radiolabeled 3α-diol in LAPC-4 cell PC model. We measured the inhibitory potency of 5α-androstane derivatives against the formation of 5α-DHT, and inhibition curves were obtained for the most potent compounds (IC50â¯=â¯1.2-14.1⯵M). The most potent inhibitor 25 (IC50â¯=â¯1.2⯵M) possesses a 4-(4-CF3-3-CH3O-benzyl)piperazinyl methyl side chain at C3ß and 17ß-OH/17α-CCH functionalities at C17 of a 5α-androstane core.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Di-Hidrotestosterona
/
Androgênios
/
Androstano-3,17-diol
Limite:
Humans
/
Male
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Canadá