Norhierridin B, a new hierridin B-based hydroquinone with improved antiproliferative activity
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/10216/130465 |
Resumo: | Hierridin B (6), a methylated hydroquinone isolated from the marine picocyanobacterium Cyanobium sp. LEGE 06113, moderately inhibited the growth of colon adenocarcinoma HT-29 cells. Aiming to improve the potential antitumor activity of this natural product, the demethylated analogue, norhierridin B (10), as well as its structurally-related quinone (9), were synthesized and evaluated for their growth inhibitory effect on a panel of human tumor cell lines, including the triple-negative breast cancer (TNBC) cells MDA-MB-231, SKBR3, and MDA-MB-468. Norhierridin B (10) showed a potent growth inhibitory effect on all cancer cell lines. Moreover, the growth inhibitory effect of compound 10 on MDA-MB-231 cells was associated with cell cycle arrest and apoptosis. Norhierridin B (10) interfered with several p53 transcriptional targets, increasing p21, Bax, and MDM2, while decreasing Bcl-2 protein levels, which suggested the potential activation of a p53 pathway. Altogether, these results evidenced a great improvement of the antitumor activity of hydroquinone 10 when compared to 6 and its structurally-related quinone (9). Notably, hydroquinone 10 displayed a prominent growth inhibitory activity against TNBC cells, which are characterized by high therapeutic resistance. |
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Norhierridin B, a new hierridin B-based hydroquinone with improved antiproliferative activityAntitumor activityHierridin BHydroquinonesQuinonesHierridin B (6), a methylated hydroquinone isolated from the marine picocyanobacterium Cyanobium sp. LEGE 06113, moderately inhibited the growth of colon adenocarcinoma HT-29 cells. Aiming to improve the potential antitumor activity of this natural product, the demethylated analogue, norhierridin B (10), as well as its structurally-related quinone (9), were synthesized and evaluated for their growth inhibitory effect on a panel of human tumor cell lines, including the triple-negative breast cancer (TNBC) cells MDA-MB-231, SKBR3, and MDA-MB-468. Norhierridin B (10) showed a potent growth inhibitory effect on all cancer cell lines. Moreover, the growth inhibitory effect of compound 10 on MDA-MB-231 cells was associated with cell cycle arrest and apoptosis. Norhierridin B (10) interfered with several p53 transcriptional targets, increasing p21, Bax, and MDM2, while decreasing Bcl-2 protein levels, which suggested the potential activation of a p53 pathway. Altogether, these results evidenced a great improvement of the antitumor activity of hydroquinone 10 when compared to 6 and its structurally-related quinone (9). Notably, hydroquinone 10 displayed a prominent growth inhibitory activity against TNBC cells, which are characterized by high therapeutic resistance.MDPI20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/130465engISSN 1420-3049https://doi.org/10.3390/molecules25071578Brandão, P.Moreira, J.Almeida, J.Nazareth, N.Sampaio-Dias, I.E.Vasconcelos, V.Martins, R.Leão, P.Pinto, M.Saraíva, L.Cidade, H.info: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:RCAAP2023-07-26T15:10:29ZPortal AgregadorONG |
dc.title.none.fl_str_mv |
Norhierridin B, a new hierridin B-based hydroquinone with improved antiproliferative activity |
title |
Norhierridin B, a new hierridin B-based hydroquinone with improved antiproliferative activity |
spellingShingle |
Norhierridin B, a new hierridin B-based hydroquinone with improved antiproliferative activity Brandão, P. Antitumor activity Hierridin B Hydroquinones Quinones |
title_short |
Norhierridin B, a new hierridin B-based hydroquinone with improved antiproliferative activity |
title_full |
Norhierridin B, a new hierridin B-based hydroquinone with improved antiproliferative activity |
title_fullStr |
Norhierridin B, a new hierridin B-based hydroquinone with improved antiproliferative activity |
title_full_unstemmed |
Norhierridin B, a new hierridin B-based hydroquinone with improved antiproliferative activity |
title_sort |
Norhierridin B, a new hierridin B-based hydroquinone with improved antiproliferative activity |
author |
Brandão, P. |
author_facet |
Brandão, P. Moreira, J. Almeida, J. Nazareth, N. Sampaio-Dias, I.E. Vasconcelos, V. Martins, R. Leão, P. Pinto, M. Saraíva, L. Cidade, H. |
author_role |
author |
author2 |
Moreira, J. Almeida, J. Nazareth, N. Sampaio-Dias, I.E. Vasconcelos, V. Martins, R. Leão, P. Pinto, M. Saraíva, L. Cidade, H. |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Brandão, P. Moreira, J. Almeida, J. Nazareth, N. Sampaio-Dias, I.E. Vasconcelos, V. Martins, R. Leão, P. Pinto, M. Saraíva, L. Cidade, H. |
dc.subject.por.fl_str_mv |
Antitumor activity Hierridin B Hydroquinones Quinones |
topic |
Antitumor activity Hierridin B Hydroquinones Quinones |
description |
Hierridin B (6), a methylated hydroquinone isolated from the marine picocyanobacterium Cyanobium sp. LEGE 06113, moderately inhibited the growth of colon adenocarcinoma HT-29 cells. Aiming to improve the potential antitumor activity of this natural product, the demethylated analogue, norhierridin B (10), as well as its structurally-related quinone (9), were synthesized and evaluated for their growth inhibitory effect on a panel of human tumor cell lines, including the triple-negative breast cancer (TNBC) cells MDA-MB-231, SKBR3, and MDA-MB-468. Norhierridin B (10) showed a potent growth inhibitory effect on all cancer cell lines. Moreover, the growth inhibitory effect of compound 10 on MDA-MB-231 cells was associated with cell cycle arrest and apoptosis. Norhierridin B (10) interfered with several p53 transcriptional targets, increasing p21, Bax, and MDM2, while decreasing Bcl-2 protein levels, which suggested the potential activation of a p53 pathway. Altogether, these results evidenced a great improvement of the antitumor activity of hydroquinone 10 when compared to 6 and its structurally-related quinone (9). Notably, hydroquinone 10 displayed a prominent growth inhibitory activity against TNBC cells, which are characterized by high therapeutic resistance. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z |
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 |
https://hdl.handle.net/10216/130465 |
url |
https://hdl.handle.net/10216/130465 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
ISSN 1420-3049 https://doi.org/10.3390/molecules25071578 |
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 |
MDPI |
publisher.none.fl_str_mv |
MDPI |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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