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 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. © 2014 Elsevier Masson SAS. All rights reserved.
Registro:
Documento: |
Artículo
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Título: | Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents |
Autor: | Sonego, J.M.; Rivero, E.M.; Gargiulo, L.; Lüthy, I.; Alvarez, L.D.; Veleiro, A.S.; Burton, G. |
Filiación: | Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, C1428EGA Ciudad de Buenos Aires, Argentina Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, C1428ADN Ciudad Autónoma de Buenos Aires, Argentina
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Palabras clave: | Antiestrogenic activity; Antiproliferative activity; Salpichrolides; Withanolides; 17(13-18)abeo 5alphah pregna 2,13,15,17 tetraen 1,20 dione; 1alpha hydroxy 17(13-18) abeo 5alphah pregna 2,13,15,17 tetraen 20 one; 20 (tert butyldimethylsilyloxy) 17 (13-18) abeo 5alphah pregna 13,15,17 trien 3beta ol; 20 acetoxy 17(13-18) abeo 5alphah pregna 2,13,15,17 tetraen 1alpha ol; 20 acetoxy 17(13-18)abeo 5alphah pregna 13,15,17 trien 3 one; 20 acetoxy 17(13-18)abeo5alphah pregna 1,13,15,17 tetraen 3 one; 20 acetoxy 1alpha,2alpha epoxy 17(13-18)abeo 5alphah pregna 13,15,17 trien 3 one; 3beta acetoxy 20 (tert butyldimethylsilyloxy) 17 (13-18)abeo 5alphah pregna 13,15,17 triene; antiestrogen; antineoplastic hormone agonists and antagonists; fulvestrant; salpichrolide A; salpichrolide B; salpichrolide derivative; salpichrolide G; unclassified drug; antiestrogen; antineoplastic hormone agonists and antagonists; ergosterol; salpichrolide A; salpichrolide B; salpichrolide G; antiestrogenic activity; antineoplastic activity; antiproliferative activity; apoptosis; article; breast cancer; cell proliferation; controlled study; cytotoxicity; drug activity; drug screening; drug structure; drug synthesis; estrogen activity; genetic algorithm; human; human cell; MCF 7 cell line; analogs and derivatives; chemical structure; chemistry; dose response; drug effects; structure activity relation; synthesis; tumor cell culture; Antineoplastic Agents, Hormonal; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Ergosterol; Estrogen Antagonists; Humans; MCF-7 Cells; Molecular Structure; Structure-Activity Relationship; Tumor Cells, Cultured |
Año: | 2014
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Volumen: | 82
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Página de inicio: | 233
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Página de fin: | 241
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DOI: |
http://dx.doi.org/10.1016/j.ejmech.2014.05.067 |
Título revista: | European Journal of Medicinal Chemistry
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Título revista abreviado: | Eur. J. Med. Chem.
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ISSN: | 02235234
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CODEN: | EJMCA
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CAS: | fulvestrant, 129453-61-8; ergosterol, 23637-22-1, 2418-45-3, 3992-98-1, 57-87-4; Antineoplastic Agents, Hormonal; Ergosterol; Estrogen Antagonists; salpichrolide A; salpichrolide B; salpichrolide G
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02235234_v82_n_p233_Sonego |
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Citas:
---------- APA ----------
Sonego, J.M., Rivero, E.M., Gargiulo, L., Lüthy, I., Alvarez, L.D., Veleiro, A.S. & Burton, G.
(2014)
. Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents. European Journal of Medicinal Chemistry, 82, 233-241.
http://dx.doi.org/10.1016/j.ejmech.2014.05.067---------- CHICAGO ----------
Sonego, J.M., Rivero, E.M., Gargiulo, L., Lüthy, I., Alvarez, L.D., Veleiro, A.S., et al.
"Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents"
. European Journal of Medicinal Chemistry 82
(2014) : 233-241.
http://dx.doi.org/10.1016/j.ejmech.2014.05.067---------- MLA ----------
Sonego, J.M., Rivero, E.M., Gargiulo, L., Lüthy, I., Alvarez, L.D., Veleiro, A.S., et al.
"Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents"
. European Journal of Medicinal Chemistry, vol. 82, 2014, pp. 233-241.
http://dx.doi.org/10.1016/j.ejmech.2014.05.067---------- VANCOUVER ----------
Sonego, J.M., Rivero, E.M., Gargiulo, L., Lüthy, I., Alvarez, L.D., Veleiro, A.S., et al. Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents. Eur. J. Med. Chem. 2014;82:233-241.
http://dx.doi.org/10.1016/j.ejmech.2014.05.067