Synthesis and biological evaluation of salpichrolide analogues as antiestrogenic agents
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 3β-acetoxy-17(13→18)-abeo-5αH-pregna...
| Autores: | , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2014 |
| País: | Argentina |
| Recursos: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/8276 |
| Acesso em linha: | http://hdl.handle.net/11336/8276 |
| Access Level: | acceso abierto |
| Palavra-chave: | Antiestrogenic Activity Salpichrolides Withanolides Antiproliferative Activity https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1 |
| Resumo: | 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 3β-acetoxy-17(13→18)-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 [3H]-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. |
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