Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IB
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.
Main Authors: | , , , , , , , , |
---|---|
Format: | Digital revista |
Language: | English |
Published: |
Sociedade Brasileira de Química
2020
|
Online Access: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532020000300536 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
id |
oai:scielo:S0103-50532020000300536 |
---|---|
record_format |
ojs |
spelling |
oai:scielo:S0103-505320200003005362020-02-27Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IBSilva,Monize M. daCamargo,Mariana S. deCastelli,SilviaGrandis,Rone A. deCastellano,Eduardo E.Deflon,Victor M.Cominetti,Marcia R.Desideri,AlessandroBatista,Alzir A. ruthenium(II) complexes mercapto ligands cytotoxicity topoisomerase IB 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.info:eu-repo/semantics/openAccessSociedade Brasileira de QuímicaJournal of the Brazilian Chemical Society v.31 n.3 20202020-03-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532020000300536en10.21577/0103-5053.20190214 |
institution |
SCIELO |
collection |
OJS |
country |
Brasil |
countrycode |
BR |
component |
Revista |
access |
En linea |
databasecode |
rev-scielo-br |
tag |
revista |
region |
America del Sur |
libraryname |
SciELO |
language |
English |
format |
Digital |
author |
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. |
spellingShingle |
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. Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IB |
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_sort |
Silva,Monize M. da |
title |
Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with 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 |
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. |
publisher |
Sociedade Brasileira de Química |
publishDate |
2020 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532020000300536 |
work_keys_str_mv |
AT silvamonizemda rutheniumiimercaptocomplexeswithanticanceractivityinteractwithtopoisomeraseib AT camargomarianasde rutheniumiimercaptocomplexeswithanticanceractivityinteractwithtopoisomeraseib AT castellisilvia rutheniumiimercaptocomplexeswithanticanceractivityinteractwithtopoisomeraseib AT grandisroneade rutheniumiimercaptocomplexeswithanticanceractivityinteractwithtopoisomeraseib AT castellanoeduardoe rutheniumiimercaptocomplexeswithanticanceractivityinteractwithtopoisomeraseib AT deflonvictorm rutheniumiimercaptocomplexeswithanticanceractivityinteractwithtopoisomeraseib AT cominettimarciar rutheniumiimercaptocomplexeswithanticanceractivityinteractwithtopoisomeraseib AT desiderialessandro rutheniumiimercaptocomplexeswithanticanceractivityinteractwithtopoisomeraseib AT batistaalzira rutheniumiimercaptocomplexeswithanticanceractivityinteractwithtopoisomeraseib |
_version_ |
1756403797904588800 |