Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase Inhibitors
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/10441 https://doi.org/10.1021/jm800945c |
Resumo: | Suppression of estrogen biosynthesis by aromatase inhibition is an effective approach for the treatment of hormone sensitive breast cancer. Third generation non-steroid aromatase inhibitors have shown important benefits in recent clinical trials with postmenopausal women. In this study we have developed a new ligand-based strategy combining important pharmacophoric and structural features according to the postulated aromatase binding mode, useful for the virtual screening of new potent non-steroid inhibitors. A small subset of promising drug candidates was identified from the large NCI database, and their antiaromatase activity was assessed on an in vitro biochemical assay with aromatase extracted from human term placenta. New potent aromatase inhibitors were discovered to be active in the low nanomolar range, and a common binding mode was proposed. These results confirm the potential of our methodology for a fast in silico high-throughput screening of potent non-steroid aromatase inhibitors. |
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Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase InhibitorsSuppression of estrogen biosynthesis by aromatase inhibition is an effective approach for the treatment of hormone sensitive breast cancer. Third generation non-steroid aromatase inhibitors have shown important benefits in recent clinical trials with postmenopausal women. In this study we have developed a new ligand-based strategy combining important pharmacophoric and structural features according to the postulated aromatase binding mode, useful for the virtual screening of new potent non-steroid inhibitors. A small subset of promising drug candidates was identified from the large NCI database, and their antiaromatase activity was assessed on an in vitro biochemical assay with aromatase extracted from human term placenta. New potent aromatase inhibitors were discovered to be active in the low nanomolar range, and a common binding mode was proposed. These results confirm the potential of our methodology for a fast in silico high-throughput screening of potent non-steroid aromatase inhibitors.American Chemical Society2009-01-08info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/10441http://hdl.handle.net/10316/10441https://doi.org/10.1021/jm800945cengJournal of Medicinal Chemistry. 52:1 (2009) 143-1500022-2623Neves, Marco A. C.Dinis, Teresa C. P.Colombo, GiorgioMelo, M. Luísa Sá einfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2020-05-29T10:05:31Zoai:estudogeral.uc.pt:10316/10441Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:47:22.438236Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase Inhibitors |
title |
Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase Inhibitors |
spellingShingle |
Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase Inhibitors Neves, Marco A. C. |
title_short |
Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase Inhibitors |
title_full |
Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase Inhibitors |
title_fullStr |
Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase Inhibitors |
title_full_unstemmed |
Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase Inhibitors |
title_sort |
Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase Inhibitors |
author |
Neves, Marco A. C. |
author_facet |
Neves, Marco A. C. Dinis, Teresa C. P. Colombo, Giorgio Melo, M. Luísa Sá e |
author_role |
author |
author2 |
Dinis, Teresa C. P. Colombo, Giorgio Melo, M. Luísa Sá e |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Neves, Marco A. C. Dinis, Teresa C. P. Colombo, Giorgio Melo, M. Luísa Sá e |
description |
Suppression of estrogen biosynthesis by aromatase inhibition is an effective approach for the treatment of hormone sensitive breast cancer. Third generation non-steroid aromatase inhibitors have shown important benefits in recent clinical trials with postmenopausal women. In this study we have developed a new ligand-based strategy combining important pharmacophoric and structural features according to the postulated aromatase binding mode, useful for the virtual screening of new potent non-steroid inhibitors. A small subset of promising drug candidates was identified from the large NCI database, and their antiaromatase activity was assessed on an in vitro biochemical assay with aromatase extracted from human term placenta. New potent aromatase inhibitors were discovered to be active in the low nanomolar range, and a common binding mode was proposed. These results confirm the potential of our methodology for a fast in silico high-throughput screening of potent non-steroid aromatase inhibitors. |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009-01-08 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/10441 http://hdl.handle.net/10316/10441 https://doi.org/10.1021/jm800945c |
url |
http://hdl.handle.net/10316/10441 https://doi.org/10.1021/jm800945c |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Medicinal Chemistry. 52:1 (2009) 143-150 0022-2623 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
American Chemical Society |
publisher.none.fl_str_mv |
American Chemical Society |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133751103455232 |