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http://www.repositorio.ufop.br/jspui/handle/123456789/11179
Título: | Synthesis, cytotoxic activity, and mode of action of new Santacruzamate A analogs. |
Autor(es): | Andrade, Silmara Nunes Evangelista, Fernanda Cristina Gontijo Seckler, Diego Eduardo Lima Marques, Deisielly Ribeiro Freitas, Tulio Resende Nunes, Renata Rachide Oliveira, Júlia Teixeira de Ribeiro, Rosy Iara Maciel de Azambuja Santos, Helio Batista dos Thomé, Ralph Gruppi Taranto, Alex Gutterres Santos, Fabio Vieira dos Viana, Gustavo Henrique Ribeiro Freitas, Rossimiriam Pereira de Humberto, Jorge Luiz Sabino, Adriano de Paula |
Palavras-chave: | Apoptosis Cancer |
Data do documento: | 2018 |
Referência: | ANDRADE, S. N. et al. Synthesis, cytotoxic activity, and mode of action of new Santacruzamate A analogs. Medicinal Chemistry Research, v. 27, n. 11/12, p. 2397–2413, dez. 2018. Disponível em: <https://link.springer.com/article/10.1007/s00044-018-2244-3>. Acesso em: 7 mar. 2019. |
Resumo: | Breast 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. |
URI: | http://www.repositorio.ufop.br/handle/123456789/11179 |
Link para o artigo: | https://link.springer.com/article/10.1007%2Fs00044-018-2244-3 |
DOI: | https://doi.org/10.1007/s00044-018-2244-3 |
ISSN: | 1554-8120 |
Aparece nas coleções: | DEQUI - Artigos publicados em periódicos |
Arquivos associados a este item:
Arquivo | Descrição | Tamanho | Formato | |
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ARTIGO_SynthesisCytotoxicActivity.pdf Restricted Access | 1,97 MB | Adobe PDF | Visualizar/Abrir |
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