Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IB

Página do item simplificado
dc.contributor.authorda Silva, Monize M.
dc.contributor.authorde Camargo, Mariana S.
dc.contributor.authorCastelli, Silvia
dc.contributor.authorde Grandis, Rone A. [UNESP]
dc.contributor.authorCastellano, Eduardo E.
dc.contributor.authorDeflon, Victor M.
dc.contributor.authorCominetti, Marcia R.
dc.contributor.authorDesideri, Alessandro
dc.contributor.authorBatista, Alzir A.
dc.contributor.institutionUniversidade Federal de São Carlos (UFSCar)
dc.contributor.institutionUniversità Tor Vergata di Roma
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2020-12-12T02:03:17Z
dc.date.available2020-12-12T02:03:17Z
dc.date.issued2020-03-01
dc.description.abstractHerein we present four new ruthenium(II) complexes: [Ru(mtz)2(dppb)] (1), [Ru(mmi)2(dppb)] (2), [Ru(dmp)2(dppb)] (3), and [Ru(mpca)2(dppb)] (4), where mtz = 2-mercaptothiazoline; mmi = 2-mercapto-1-methyl-imidazole; dmp = 4,6-diamino-2 - m e r c a p t o p y r i m i d i n e; m p c a = 6 - m e r c a p t o p y r i d i n e - 3 - c a r b o x y l i c a c i d; dppb = 1,4-bis(diphenylphosphino)butane. In vitro cell culture experiments revealed cytotoxic activity for complexes 2, 3 and 4 against MCF-7 (breast, non-invasive), MDA-MB-231 (breast, invasive), A549 (lung), DU-145 (prostate) and HepG2 (liver) tumor cells, in some cases lower than the half maximal inhibitory concentration (IC50) for the reference drug (cisplatin). The deoxyribonucleic acid (DNA) interactions studied by viscosity measurements, gel electrophoresis and square-wave voltammetry indicated that the DNA binding affinity primarily occurs through non-covalent interactions. Only complex 2 was able to fully inhibit the DNA supercoiled relaxation mediated by human topoisomerase IB (Top IB). The analysis indicates that complex 2 inhibits the cleavage and the reconnection steps of the catalytic cycle, being both a poison and a catalytic inhibitor.en
dc.description.affiliationDepartamento de Química Universidade Federal de São Carlos, CP 676
dc.description.affiliationDipartimento di Biologia Università Tor Vergata di Roma
dc.description.affiliationDepartamento de Ciências Biológicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista (Unesp)
dc.description.affiliationInstituto de Física de São Carlos Universidade de São Paulo, CP 369
dc.description.affiliationInstituto de Química de São Carlos Universidade de São Paulo, CP 780
dc.description.affiliationDepartamento de Gerontologia Universidade Federal de São Carlos, CP 676
dc.description.affiliationUnespDepartamento de Ciências Biológicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista (Unesp)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent536-549
dc.identifierhttp://dx.doi.org/10.21577/0103-5053.20190214
dc.identifier.citationJournal of the Brazilian Chemical Society, v. 31, n. 3, p. 536-549, 2020.
dc.identifier.doi10.21577/0103-5053.20190214
dc.identifier.fileS0103-50532020000300536.pdf
dc.identifier.issn1678-4790
dc.identifier.issn0103-5053
dc.identifier.scieloS0103-50532020000300536
dc.identifier.scopus2-s2.0-85083674896
dc.identifier.urihttp://hdl.handle.net/11449/200311
dc.language.isoeng
dc.relation.ispartofJournal of the Brazilian Chemical Society
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectCytotoxicity
dc.subjectMercapto ligands
dc.subjectRuthenium(II) complexes
dc.subjectTopoisomerase IB
dc.titleRuthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IBen
dc.typeArtigo

Arquivos

Pacote Original
Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
S0103-50532020000300536.pdf
Tamanho:
4.81 MB
Formato:
Adobe Portable Document Format
Baixar

Coleções

Artigos - Ciências Biológicas - FCFAR