Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents.
Eur J Med Chem
; 82: 233-41, 2014 Jul 23.
Article
em En
| MEDLINE
| ID: mdl-24908652
ABSTRACT
The antiestrogenic activity of three natural salpichrolides A, G and B (1, 3 and 4) and of five synthetic analogs containing an aromatic D ring and a simplified side chain (5-9), was evaluated on MCF-7 cells. The 2,3-ene-1-keto steroids 8 and 9 were obtained from 3ß-acetoxy-17(13â18)-abeo-5αH-pregna-13,15,17-trien-20-one, the key step for these syntheses being a Wharton carbonyl rearrangement of a 1,2-epoxy-3-keto steroid to the allylic alcohol using hydrazine hydrate. The antiestrogenic activity was evaluated by performing dose-response experiments in ER(+) MCF-7 breast cancer cells. Dose-dependent proliferation was quantified via [(3)H]-thymidine incorporation after 3 days treatment. Salpichrolides A, G and B and analogs 5, 8 and 9 were active as antiestrogens with compound 9 being the most active of the synthetic analogs. Compounds 5 and 9 were also evaluated against the ER(-) cell line MDA-MB-231 and shown to be inactive.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antineoplásicos Hormonais
/
Ergosterol
/
Antagonistas de Estrogênios
Limite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Argentina