Synthesis, cytotoxic activity, and mode of action of new Santacruzamate A analogs.

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MetadadosDescriçãoIdioma
Autor(es): dc.creatorAndrade, Silmara Nunes-
Autor(es): dc.creatorEvangelista, Fernanda Cristina Gontijo-
Autor(es): dc.creatorSeckler, Diego Eduardo Lima-
Autor(es): dc.creatorMarques, Deisielly Ribeiro-
Autor(es): dc.creatorFreitas, Tulio Resende-
Autor(es): dc.creatorNunes, Renata Rachide-
Autor(es): dc.creatorOliveira, Júlia Teixeira de-
Autor(es): dc.creatorRibeiro, Rosy Iara Maciel de Azambuja-
Autor(es): dc.creatorSantos, Helio Batista dos-
Autor(es): dc.creatorThomé, Ralph Gruppi-
Autor(es): dc.creatorTaranto, Alex Gutterres-
Autor(es): dc.creatorSantos, Fabio Vieira dos-
Autor(es): dc.creatorViana, Gustavo Henrique Ribeiro-
Autor(es): dc.creatorFreitas, Rossimiriam Pereira de-
Autor(es): dc.creatorHumberto, Jorge Luiz-
Autor(es): dc.creatorSabino, Adriano de Paula-
Data de aceite: dc.date.accessioned2025-08-21T15:32:22Z-
Data de disponibilização: dc.date.available2025-08-21T15:32:22Z-
Data de envio: dc.date.issued2019-05-03-
Data de envio: dc.date.issued2019-05-03-
Data de envio: dc.date.issued2018-
Fonte completa do material: dc.identifierhttp://www.repositorio.ufop.br/handle/123456789/11179-
Fonte completa do material: dc.identifierhttps://link.springer.com/article/10.1007%2Fs00044-018-2244-3-
Fonte completa do material: dc.identifierhttps://doi.org/10.1007/s00044-018-2244-3-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/1017777-
Descrição: dc.descriptionBreast and ovarian cancer are the most common cancers in women. Available cancer treatments, in general, have limited efficacy and frequent, undesirable side effects. Recently, scientists have focused on searching for new epigenetic modulators such as inhibitors of DNA methyltransferases and histone deacetylases (HDACs), with novel properties and selectivity. We report the synthesis of seven new analogs of Santacruzamate A. Molecular modeling showed that compounds 3–9 presented the best binding energies (kcal/mol) against HDAC4 compared to that of crystallographic ligand. The compounds were evaluated against MCF-7 and MDA-MB-231 (breast cancer), TOV-21G (ovarian adenocarcinoma), and WI-26VA4 (non-tumor lung fibroblasts) cells. Compound 5, the most potent and selective of the series, exhibited remarkably enhanced anticancer potency, with IC50 values for the tumor cells of 24.3–44.93 μM, compared with that of etoposide (12–18.57 μM) and doxorubicin (2.1–4.37 μM). Further investigation showed that compound 5 could promote DNA damage, increase the activity of caspases-3 and -9, and upregulate mRNA levels of p21, TP53, and BAK, suggesting apoptotic cell death of the tumor cells via the intrinsic pathway. This study demonstrated that synthetic analogs of santacruzamate A with zinc-linked groups are effective for improving both HDAC inhibition and antitumor activity.-
Formato: dc.formatapplication/pdf-
Idioma: dc.languageen-
Direitos: dc.rightsrestrito-
Palavras-chave: dc.subjectApoptosis-
Palavras-chave: dc.subjectCancer-
Título: dc.titleSynthesis, cytotoxic activity, and mode of action of new Santacruzamate A analogs.-
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