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Title: Non-mutagenic Ru(II) complexes : cytotoxicity, topoisomerase IB inhibition, DNA and HSA binding.
Authors: Silva, Monize Martins da
Camargo, Mariana Santoro de
Correa, Rodrigo de Souza
Castelli, Silvia
Grandis, Rone De
Takarada, Jéssica Emi
Varanda, Eliana Aparecida
Castellano, Eduardo Ernesto
Deflon, Victor Marcelo
Cominetti, Márcia Regina
Desideri, Alessandro
Batista, Alzir Azevedo
Issue Date: 2019
Citation: SILVA, M. M. et al. Non-mutagenic Ru(II) complexes: cytotoxicity, topoisomerase IB inhibition, DNA and HSA binding. Dalton Transactions, v. 48, p. 14885-14897, set. 2019. Disponível em: <!divAbstract>. Acesso em: 10 fev. 2020.
Abstract: Herein 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.
metadata.dc.identifier.doi: 10.1039/c9dt01905g
ISSN: 1477-9234
Appears in Collections:DEQUI - Artigos publicados em periódicos

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