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

Detalhes bibliográficos
Autor(a) principal: Silva,Monize M. da
Data de Publicação: 2020
Outros Autores: Camargo,Mariana S. de, Castelli,Silvia, Grandis,Rone A. de, Castellano,Eduardo E., Deflon,Victor M., Cominetti,Marcia R., Desideri,Alessandro, Batista,Alzir A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Journal of the Brazilian Chemical Society (Online)
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532020000300536
Resumo: Herein 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-mercaptopyrimidine; mpca = 6-mercaptopyridine-3-carboxylic acid; 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.
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spelling Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IBruthenium(II) complexesmercapto ligandscytotoxicitytopoisomerase IBHerein 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-mercaptopyrimidine; mpca = 6-mercaptopyridine-3-carboxylic acid; 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.Sociedade Brasileira de Química2020-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532020000300536Journal of the Brazilian Chemical Society v.31 n.3 2020reponame:Journal of the Brazilian Chemical Society (Online)instname:Sociedade Brasileira de Química (SBQ)instacron:SBQ10.21577/0103-5053.20190214info:eu-repo/semantics/openAccessSilva,Monize M. daCamargo,Mariana S. deCastelli,SilviaGrandis,Rone A. deCastellano,Eduardo E.Deflon,Victor M.Cominetti,Marcia R.Desideri,AlessandroBatista,Alzir A.eng2020-02-27T00:00:00Zoai:scielo:S0103-50532020000300536Revistahttp://jbcs.sbq.org.brONGhttps://old.scielo.br/oai/scielo-oai.php||office@jbcs.sbq.org.br1678-47900103-5053opendoar:2020-02-27T00:00Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)false
dc.title.none.fl_str_mv Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IB
title Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IB
spellingShingle Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IB
Silva,Monize M. da
ruthenium(II) complexes
mercapto ligands
cytotoxicity
topoisomerase IB
title_short Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IB
title_full Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IB
title_fullStr Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IB
title_full_unstemmed Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IB
title_sort Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IB
author Silva,Monize M. da
author_facet Silva,Monize M. da
Camargo,Mariana S. de
Castelli,Silvia
Grandis,Rone A. de
Castellano,Eduardo E.
Deflon,Victor M.
Cominetti,Marcia R.
Desideri,Alessandro
Batista,Alzir A.
author_role author
author2 Camargo,Mariana S. de
Castelli,Silvia
Grandis,Rone A. de
Castellano,Eduardo E.
Deflon,Victor M.
Cominetti,Marcia R.
Desideri,Alessandro
Batista,Alzir A.
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Silva,Monize M. da
Camargo,Mariana S. de
Castelli,Silvia
Grandis,Rone A. de
Castellano,Eduardo E.
Deflon,Victor M.
Cominetti,Marcia R.
Desideri,Alessandro
Batista,Alzir A.
dc.subject.por.fl_str_mv ruthenium(II) complexes
mercapto ligands
cytotoxicity
topoisomerase IB
topic ruthenium(II) complexes
mercapto ligands
cytotoxicity
topoisomerase IB
description Herein 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-mercaptopyrimidine; mpca = 6-mercaptopyridine-3-carboxylic acid; 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.
publishDate 2020
dc.date.none.fl_str_mv 2020-03-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532020000300536
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532020000300536
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.21577/0103-5053.20190214
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Sociedade Brasileira de Química
publisher.none.fl_str_mv Sociedade Brasileira de Química
dc.source.none.fl_str_mv Journal of the Brazilian Chemical Society v.31 n.3 2020
reponame:Journal of the Brazilian Chemical Society (Online)
instname:Sociedade Brasileira de Química (SBQ)
instacron:SBQ
instname_str Sociedade Brasileira de Química (SBQ)
instacron_str SBQ
institution SBQ
reponame_str Journal of the Brazilian Chemical Society (Online)
collection Journal of the Brazilian Chemical Society (Online)
repository.name.fl_str_mv Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)
repository.mail.fl_str_mv ||office@jbcs.sbq.org.br
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