Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IB
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , |
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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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 |
_version_ |
1750318182645628928 |