Non-mutagenic Ru(ii) complexes: Cytotoxicity, topoisomerase IB inhibition, DNA and HSA binding

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Autor(es): dc.contributorUniversitàTorVergatadi Roma-
Autor(es): dc.contributorUniversidade Federal de São Carlos (UFSCar)-
Autor(es): dc.contributorUniversidade Federal de Ouro Preto-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUniversidade DeSão Paulo-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.creatorDa Silva, Monize M.-
Autor(es): dc.creatorDe Camargo, Mariana S.-
Autor(es): dc.creatorCorrea, Rodrigo S.-
Autor(es): dc.creatorCastelli, Silvia-
Autor(es): dc.creatorDe Grandis, Rone A. [UNESP]-
Autor(es): dc.creatorTakarada, Jessica E.-
Autor(es): dc.creatorVaranda, Eliana A. [UNESP]-
Autor(es): dc.creatorCastellano, Eduardo E.-
Autor(es): dc.creatorDeflon, Victor M.-
Autor(es): dc.creatorCominetti, Marcia R.-
Autor(es): dc.creatorDesideri, Alessandro-
Autor(es): dc.creatorBatista, Alzir A.-
Data de aceite: dc.date.accessioned2022-02-22T00:27:27Z-
Data de disponibilização: dc.date.available2022-02-22T00:27:27Z-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2019-01-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1039/c9dt01905g-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/199469-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/199469-
Descrição: dc.descriptionHerein we discuss five ruthenium(ii) complexes with good cytotoxicity against cancer cells. These complexes are named [Ru(tzdt)(bipy)(dppb)]PF6 (1), [Ru(mmi)(bipy)(dppb)]PF6 (2), [Ru(dmp)(bipy)(dppb)]PF6 (3), [Ru(mpca)(bipy)(dppb)]PF6 (4) and [Ru(2mq)(bipy)(dppb)]PF6 (5), where tzdt = 1,3-thiazolidine-2-thione, mmi = mercapto-1-methyl-imidazole, dmp = 4,6-diamino-2-mercaptopyrimidine, mpca = 6-mercaptopyridine-3-carboxylic acid, 2mq = 2-mercapto-4(3H)-quinazolinone, bipy = 2,2′-bipyridine and dppb = 1,4-bis(diphenylphosphino)butane. In vitro cell culture experiments revealed significant cytotoxic activity for 1-5 against MDA-MB-231, MCF-7, A549, DU-145 and HepG2 tumor cells, higher than that for the standard anticancer drug cisplatin. Compound/DNA interaction studies were carried out showing that 1-5 interact with DNA by electrostatic force of attraction or by hydrogen bonding. Moreover, the complexes interact, moderately and spontaneously, with human serum albumin (HSA) through the hydrophobic region. The five complexes are able to inhibit the DNA supercoiled relaxation mediated by human topoisomerase IB (TopIB), and complex 1 is found to be the most efficient TopIB inhibitor among the five compounds. The inhibitory effect and analysis of different steps of the TopIB catalytic cycle indicate that complex 1 inhibits the cleavage reaction impeding the binding of the enzyme to DNA and has no effect on the religation step. Complexes 1, 2 and 3 did not show mutagenic activity when they were evaluated by the cytokinesis-block micronucleus cytome assay in HepG2 cells and the Ames test in the presence and absence of mouse liver S9 metabolic activation. Therefore, it is necessary to perform further in-depth analysis of the therapeutic potential of these promising ruthenium complexes as anticancer drugs.-
Descrição: dc.descriptionDipartimentodi Biologia UniversitàTorVergatadi Roma-
Descrição: dc.descriptionDepartamento de Química Universidade Federal de São Carlos, CP 676-
Descrição: dc.descriptionDepartamento de Química Universidade Federal de Ouro Preto-
Descrição: dc.descriptionDepartamento de Ciências Biológicas Faculdade de Ciências Farmacêuticas UNESP-
Descrição: dc.descriptionInstituto de Física Universidade DeSão Paulo, CP 369-
Descrição: dc.descriptionInstituto de Química de São Carlos Universidade de São Paulo, CP 780-
Descrição: dc.descriptionDepartamento de Gerontologia Universidade Federal de São Carlos, CP 676-
Descrição: dc.descriptionDepartamento de Ciências Biológicas Faculdade de Ciências Farmacêuticas UNESP-
Formato: dc.format14885-14897-
Idioma: dc.languageen-
Relação: dc.relationDalton Transactions-
???dc.source???: dc.sourceScopus-
Título: dc.titleNon-mutagenic Ru(ii) complexes: Cytotoxicity, topoisomerase IB inhibition, DNA and HSA binding-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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