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Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/70590
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dc.creatorSilmara Nunes Andradept_BR
dc.creatorFernanda Cristina Gontijo Evangelistapt_BR
dc.creatorDiego Eduardo Lima Secklerpt_BR
dc.creatorDeisielly Ribeiro Marquespt_BR
dc.creatorTúlio Resende Freitaspt_BR
dc.creatorRenata Rachide Nunespt_BR
dc.creatorJúlia Teixeira de Oliveirapt_BR
dc.creatorRosy Iara Maciel de Azambuja Ribeiropt_BR
dc.creatorHélio Batista dos Santospt_BR
dc.creatorRalph Gruppi Thomépt_BR
dc.creatorAlex Gutterres Tarantopt_BR
dc.creatorFabio Vieira dos Santospt_BR
dc.creatorGustavo Henrique Ribeiro Vianapt_BR
dc.creatorRossimiriam Pereira de Freitaspt_BR
dc.creatorJorge Luiz Humbertopt_BR
dc.creatorAdriano de Paula Sabinopt_BR
dc.creatorFlaviane Francisco Hiláriopt_BR
dc.creatorFernando de Pilla Varottipt_BR
dc.date.accessioned2024-07-15T19:16:49Z-
dc.date.available2024-07-15T19:16:49Z-
dc.date.issued2018-
dc.citation.volume27pt_BR
dc.citation.issue11-12pt_BR
dc.citation.spage2397pt_BR
dc.citation.epage2413pt_BR
dc.identifier.doihttps://doi.org/10.1007/s00044-018-2244-3pt_BR
dc.identifier.issn1554-8120pt_BR
dc.identifier.urihttp://hdl.handle.net/1843/70590-
dc.description.resumoBreast 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.pt_BR
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Geraispt_BR
dc.languageengpt_BR
dc.publisherUniversidade Federal de Minas Geraispt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.departmentFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICASpt_BR
dc.publisher.departmentICX - DEPARTAMENTO DE QUÍMICApt_BR
dc.publisher.initialsUFMGpt_BR
dc.relation.ispartofMedical Chemistry Researchpt_BR
dc.rightsAcesso Restritopt_BR
dc.subjectSantacruzamate A analogspt_BR
dc.subjectCytotoxicitypt_BR
dc.subjectMode of actionpt_BR
dc.subjectApoptosispt_BR
dc.subjectCancerpt_BR
dc.subject.otherQuímica farmacêuticapt_BR
dc.subject.otherAgentes antineoplásicospt_BR
dc.subject.otherApoptosept_BR
dc.subject.otherCitotoxidade de mediação celularpt_BR
dc.subject.otherMecanismo de ação (Bioquímica)pt_BR
dc.subject.otherSíntesept_BR
dc.titleSynthesis, cytotoxic activity, and mode of action of new Santacruzamate A analogspt_BR
dc.typeArtigo de Periódicopt_BR
dc.url.externahttps://link.springer.com/article/10.1007/s00044-018-2244-3pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-1975-0827pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0003-4682-397Xpt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-1430-4799pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-2289-2201pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-1239-5412pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-7374-4743pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0001-6813-8522pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-1779-5036pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-6086-1043pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-1521-7486pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0001-6974-3724pt_BR
dc.identifier.orcidhttps://orcid.org/0009-0001-9688-1812pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0001-8562-8689pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-2939-7780pt_BR
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