Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone
Autor(a) principal: | |
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Data de Publicação: | 2010 |
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/10400.13/5013 |
Resumo: | Naturally occurring xanthones have been docu mented as having antitumor properties, with some of them presently undergoing clinical trials. In an attempt to improve the biological activities of dihydroxyxanthones, prenylation and other mole cular modifications were performed. All the com pounds reduced viable cell number in a leukemia cell line K-562, with the fused xanthone 3, 4-dihydro-12-hydroxy-2,2-dimethyl-2H,6H-pyrano[3, 2-b]xanthen-6-one (5) being the most potent. The pyranoxanthone 5 was particularly effective in additional leukemia cell lines (HL-60 and BV-173). Furthermore, the pyranoxanthone 5 decreased cel lular proliferation and induced an S-phase cell cycle arrest. In vitro, the pyranoxanthone 5 increased the percentage of apoptotic cells which was confirmed by an appropriate response at the protein level (e.g., PARP cleavage). Using a com puter screening strategy based on the structure of several anti- and pro-apoptotic proteins, it was verified that the pyranoxanthone 5 may block the binding of anti-apoptotic Bcl-xL to pro-apoptotic Bad and Bim. The structure-based screening revealed the pyranoxanthone 5 as a new scaffold that may guide the design of small molecules with better affinity profile for Bcl-xL. |
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Insights into the in vitro antitumor mechanism of action of a new pyranoxanthoneAntiproliferationApoptosisBcl-xLLeukemiaStructure-based screeningXanthone.Faculdade de Ciências Exatas e da EngenhariaNaturally occurring xanthones have been docu mented as having antitumor properties, with some of them presently undergoing clinical trials. In an attempt to improve the biological activities of dihydroxyxanthones, prenylation and other mole cular modifications were performed. All the com pounds reduced viable cell number in a leukemia cell line K-562, with the fused xanthone 3, 4-dihydro-12-hydroxy-2,2-dimethyl-2H,6H-pyrano[3, 2-b]xanthen-6-one (5) being the most potent. The pyranoxanthone 5 was particularly effective in additional leukemia cell lines (HL-60 and BV-173). Furthermore, the pyranoxanthone 5 decreased cel lular proliferation and induced an S-phase cell cycle arrest. In vitro, the pyranoxanthone 5 increased the percentage of apoptotic cells which was confirmed by an appropriate response at the protein level (e.g., PARP cleavage). Using a com puter screening strategy based on the structure of several anti- and pro-apoptotic proteins, it was verified that the pyranoxanthone 5 may block the binding of anti-apoptotic Bcl-xL to pro-apoptotic Bad and Bim. The structure-based screening revealed the pyranoxanthone 5 as a new scaffold that may guide the design of small molecules with better affinity profile for Bcl-xL.WileyDigitUMaPalmeira, AndreiaPaiva, AnaSousa, EmíliaSeca, HugoAlmeida, Gabriela M.Lima, Raquel T.Fernandes, Miguel X.Pinto, MadalenaVasconcelos, M. Helena2023-02-08T11:29:22Z20102010-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.13/5013engPalmeira, A., Paiva, A., Sousa, E., Seca, H., Almeida, G. M., Lima, R. T., ... & Vasconcelos, M. H. (2010). Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone. Chemical biology & drug design, 76(1), 43-58.10.1111/j.1747-0285.2010.00978.xinfo: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:RCAAP2023-03-12T05:24:10Zoai:digituma.uma.pt:10400.13/5013Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:46:29.410474Repositório 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 |
Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone |
title |
Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone |
spellingShingle |
Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone Palmeira, Andreia Antiproliferation Apoptosis Bcl-xL Leukemia Structure-based screening Xanthone . Faculdade de Ciências Exatas e da Engenharia |
title_short |
Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone |
title_full |
Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone |
title_fullStr |
Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone |
title_full_unstemmed |
Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone |
title_sort |
Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone |
author |
Palmeira, Andreia |
author_facet |
Palmeira, Andreia Paiva, Ana Sousa, Emília Seca, Hugo Almeida, Gabriela M. Lima, Raquel T. Fernandes, Miguel X. Pinto, Madalena Vasconcelos, M. Helena |
author_role |
author |
author2 |
Paiva, Ana Sousa, Emília Seca, Hugo Almeida, Gabriela M. Lima, Raquel T. Fernandes, Miguel X. Pinto, Madalena Vasconcelos, M. Helena |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
DigitUMa |
dc.contributor.author.fl_str_mv |
Palmeira, Andreia Paiva, Ana Sousa, Emília Seca, Hugo Almeida, Gabriela M. Lima, Raquel T. Fernandes, Miguel X. Pinto, Madalena Vasconcelos, M. Helena |
dc.subject.por.fl_str_mv |
Antiproliferation Apoptosis Bcl-xL Leukemia Structure-based screening Xanthone . Faculdade de Ciências Exatas e da Engenharia |
topic |
Antiproliferation Apoptosis Bcl-xL Leukemia Structure-based screening Xanthone . Faculdade de Ciências Exatas e da Engenharia |
description |
Naturally occurring xanthones have been docu mented as having antitumor properties, with some of them presently undergoing clinical trials. In an attempt to improve the biological activities of dihydroxyxanthones, prenylation and other mole cular modifications were performed. All the com pounds reduced viable cell number in a leukemia cell line K-562, with the fused xanthone 3, 4-dihydro-12-hydroxy-2,2-dimethyl-2H,6H-pyrano[3, 2-b]xanthen-6-one (5) being the most potent. The pyranoxanthone 5 was particularly effective in additional leukemia cell lines (HL-60 and BV-173). Furthermore, the pyranoxanthone 5 decreased cel lular proliferation and induced an S-phase cell cycle arrest. In vitro, the pyranoxanthone 5 increased the percentage of apoptotic cells which was confirmed by an appropriate response at the protein level (e.g., PARP cleavage). Using a com puter screening strategy based on the structure of several anti- and pro-apoptotic proteins, it was verified that the pyranoxanthone 5 may block the binding of anti-apoptotic Bcl-xL to pro-apoptotic Bad and Bim. The structure-based screening revealed the pyranoxanthone 5 as a new scaffold that may guide the design of small molecules with better affinity profile for Bcl-xL. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010 2010-01-01T00:00:00Z 2023-02-08T11:29:22Z |
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/10400.13/5013 |
url |
http://hdl.handle.net/10400.13/5013 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Palmeira, A., Paiva, A., Sousa, E., Seca, H., Almeida, G. M., Lima, R. T., ... & Vasconcelos, M. H. (2010). Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone. Chemical biology & drug design, 76(1), 43-58. 10.1111/j.1747-0285.2010.00978.x |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Wiley |
publisher.none.fl_str_mv |
Wiley |
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 |
repository.mail.fl_str_mv |
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1799130936439209984 |