Synthesis and biological evaluation of salpichrolide analogs 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-pregn...
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2014
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02235234_v82_n_p233_Sonego http://hdl.handle.net/20.500.12110/paper_02235234_v82_n_p233_Sonego |
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paper:paper_02235234_v82_n_p233_Sonego2023-06-08T15:21:47Z Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents Sonego, Juan Manuel Lüthy, Isabel Alicia Veleiro, Adriana Silvia Burton, Gerardo 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 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. Fil:Sonego, J.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Lüthy, I. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Veleiro, A.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Burton, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02235234_v82_n_p233_Sonego http://hdl.handle.net/20.500.12110/paper_02235234_v82_n_p233_Sonego |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Sonego, Juan Manuel Lüthy, Isabel Alicia Veleiro, Adriana Silvia Burton, Gerardo Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents |
| topic_facet |
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 |
| description |
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. |
| author |
Sonego, Juan Manuel Lüthy, Isabel Alicia Veleiro, Adriana Silvia Burton, Gerardo |
| author_facet |
Sonego, Juan Manuel Lüthy, Isabel Alicia Veleiro, Adriana Silvia Burton, Gerardo |
| author_sort |
Sonego, Juan Manuel |
| title |
Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents |
| title_short |
Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents |
| title_full |
Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents |
| title_fullStr |
Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents |
| title_full_unstemmed |
Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents |
| title_sort |
synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents |
| publishDate |
2014 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02235234_v82_n_p233_Sonego http://hdl.handle.net/20.500.12110/paper_02235234_v82_n_p233_Sonego |
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AT sonegojuanmanuel synthesisandbiologicalevaluationofsalpichrolideanalogsasantiestrogenicagents AT luthyisabelalicia synthesisandbiologicalevaluationofsalpichrolideanalogsasantiestrogenicagents AT veleiroadrianasilvia synthesisandbiologicalevaluationofsalpichrolideanalogsasantiestrogenicagents AT burtongerardo synthesisandbiologicalevaluationofsalpichrolideanalogsasantiestrogenicagents |
| _version_ |
1768546157261225984 |