Sulfonamide-containing copper(II) metallonucleases: Correlations with in vitro antimycobacterial and antiproliferative activities

Detalhes bibliográficos
Autor(a) principal: Nakahata, Douglas H.
Data de Publicação: 2018
Outros Autores: de Paiva, Raphael E.F., Lustri, Wilton R., Ribeiro, Camila M. [UNESP], Pavan, Fernando R. [UNESP], da Silva, Gisele G., Ruiz, Ana L.T.G., de Carvalho, João E., Corbi, Pedro P.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.jinorgbio.2018.07.011
http://hdl.handle.net/11449/180073
Resumo: The bis-(1,10-phenanthroline)copper(I) complex, [Cu(I)(phen)2]+, was the first copper-based artificial nuclease reported in the literature. The biological and ligand-like properties of sulfonamides make them good candidates for fine-tuning the reactivity of the [Cu(phen)2] motif with biomolecules. In this context, we developed three novel copper(II) complexes containing the sulfonamides sulfameter (smtrH) and sulfadimethoxine (sdmxH) and (N^N)-bidentate ligands (2,2′-biyridine or 1,10-phenantroline). The compounds were characterized by chemical and spectroscopic techniques and single-crystal X-ray crystallography. When targeting plasmid DNA, the phen-containing compounds [Cu(smtr−)2(phen)] (1) and [Cu(sdmx−)2(phen)] (2) demonstrated nuclease activity even in the absence of reducing agents. Addition of ascorbic acid resulted in a complete cleavage of DNA by 1 and 2 at concentrations higher than 10 μM. Experiments designed to evaluate the copper intermediates involved in the nuclease effect after reaction with ascorbic acid identified at least the [Cu(I)(N^N)2]+, [Cu(I)(sulfa)(N^N)]+ and [Cu(I)(sulfa)2]+ species. The compounds interact with DNA via groove binding and intercalation as verified by fluorescence spectroscopy, circular dichroism (CD) and molecular docking. The magnitude and preferred mode of binding are dependent on the nature of both N^N ligand and the sulfonamide. The potent nuclease activity of compounds 1 and 2 are well correlated with their antiproliferative and anti-M. tuberculosis profiles. The results presented here demonstrated the potential for further development of copper(II)-sulfonamide-(N^N) complexes as multipurpose metallodrugs.
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spelling Sulfonamide-containing copper(II) metallonucleases: Correlations with in vitro antimycobacterial and antiproliferative activitiesAnti-M. tuberculosis activityAntiproliferative activityCopper(II)MetallonucleasesSulfonamidesThe bis-(1,10-phenanthroline)copper(I) complex, [Cu(I)(phen)2]+, was the first copper-based artificial nuclease reported in the literature. The biological and ligand-like properties of sulfonamides make them good candidates for fine-tuning the reactivity of the [Cu(phen)2] motif with biomolecules. In this context, we developed three novel copper(II) complexes containing the sulfonamides sulfameter (smtrH) and sulfadimethoxine (sdmxH) and (N^N)-bidentate ligands (2,2′-biyridine or 1,10-phenantroline). The compounds were characterized by chemical and spectroscopic techniques and single-crystal X-ray crystallography. When targeting plasmid DNA, the phen-containing compounds [Cu(smtr−)2(phen)] (1) and [Cu(sdmx−)2(phen)] (2) demonstrated nuclease activity even in the absence of reducing agents. Addition of ascorbic acid resulted in a complete cleavage of DNA by 1 and 2 at concentrations higher than 10 μM. Experiments designed to evaluate the copper intermediates involved in the nuclease effect after reaction with ascorbic acid identified at least the [Cu(I)(N^N)2]+, [Cu(I)(sulfa)(N^N)]+ and [Cu(I)(sulfa)2]+ species. The compounds interact with DNA via groove binding and intercalation as verified by fluorescence spectroscopy, circular dichroism (CD) and molecular docking. The magnitude and preferred mode of binding are dependent on the nature of both N^N ligand and the sulfonamide. The potent nuclease activity of compounds 1 and 2 are well correlated with their antiproliferative and anti-M. tuberculosis profiles. The results presented here demonstrated the potential for further development of copper(II)-sulfonamide-(N^N) complexes as multipurpose metallodrugs.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Institute of Chemistry University of Campinas UNICAMPBiological and Health Sciences Department University of Araraquara UNIARASchool of Pharmaceutical Sciences São Paulo State University UNESPFaculty of Pharmaceutical Sciences University of Campinas UNICAMPChemical Biological and Agricultural Pluridisciplinary Research Center (CPQBA) University of Campinas – UNICAMPDepartment of Physiological Sciences Piracicaba Dental School University of Campinas UNICAMPSchool of Pharmaceutical Sciences São Paulo State University UNESPCNPq: 140466/2014-2FAPESP: 2015/09833-0FAPESP: 2015/20882-3FAPESP: 2015/25114-4CNPq: 442123/2014-0Universidade Estadual de Campinas (UNICAMP)UNIARAUniversidade Estadual Paulista (Unesp)Nakahata, Douglas H.de Paiva, Raphael E.F.Lustri, Wilton R.Ribeiro, Camila M. [UNESP]Pavan, Fernando R. [UNESP]da Silva, Gisele G.Ruiz, Ana L.T.G.de Carvalho, João E.Corbi, Pedro P.2018-12-11T17:37:54Z2018-12-11T17:37:54Z2018-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article85-96application/pdfhttp://dx.doi.org/10.1016/j.jinorgbio.2018.07.011Journal of Inorganic Biochemistry, v. 187, p. 85-96.1873-33440162-0134http://hdl.handle.net/11449/18007310.1016/j.jinorgbio.2018.07.0112-s2.0-850508927912-s2.0-85050892791.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Inorganic Biochemistry0,743info:eu-repo/semantics/openAccess2024-06-24T13:07:37Zoai:repositorio.unesp.br:11449/180073Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T17:37:51.592210Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Sulfonamide-containing copper(II) metallonucleases: Correlations with in vitro antimycobacterial and antiproliferative activities
title Sulfonamide-containing copper(II) metallonucleases: Correlations with in vitro antimycobacterial and antiproliferative activities
spellingShingle Sulfonamide-containing copper(II) metallonucleases: Correlations with in vitro antimycobacterial and antiproliferative activities
Nakahata, Douglas H.
Anti-M. tuberculosis activity
Antiproliferative activity
Copper(II)
Metallonucleases
Sulfonamides
title_short Sulfonamide-containing copper(II) metallonucleases: Correlations with in vitro antimycobacterial and antiproliferative activities
title_full Sulfonamide-containing copper(II) metallonucleases: Correlations with in vitro antimycobacterial and antiproliferative activities
title_fullStr Sulfonamide-containing copper(II) metallonucleases: Correlations with in vitro antimycobacterial and antiproliferative activities
title_full_unstemmed Sulfonamide-containing copper(II) metallonucleases: Correlations with in vitro antimycobacterial and antiproliferative activities
title_sort Sulfonamide-containing copper(II) metallonucleases: Correlations with in vitro antimycobacterial and antiproliferative activities
author Nakahata, Douglas H.
author_facet Nakahata, Douglas H.
de Paiva, Raphael E.F.
Lustri, Wilton R.
Ribeiro, Camila M. [UNESP]
Pavan, Fernando R. [UNESP]
da Silva, Gisele G.
Ruiz, Ana L.T.G.
de Carvalho, João E.
Corbi, Pedro P.
author_role author
author2 de Paiva, Raphael E.F.
Lustri, Wilton R.
Ribeiro, Camila M. [UNESP]
Pavan, Fernando R. [UNESP]
da Silva, Gisele G.
Ruiz, Ana L.T.G.
de Carvalho, João E.
Corbi, Pedro P.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual de Campinas (UNICAMP)
UNIARA
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Nakahata, Douglas H.
de Paiva, Raphael E.F.
Lustri, Wilton R.
Ribeiro, Camila M. [UNESP]
Pavan, Fernando R. [UNESP]
da Silva, Gisele G.
Ruiz, Ana L.T.G.
de Carvalho, João E.
Corbi, Pedro P.
dc.subject.por.fl_str_mv Anti-M. tuberculosis activity
Antiproliferative activity
Copper(II)
Metallonucleases
Sulfonamides
topic Anti-M. tuberculosis activity
Antiproliferative activity
Copper(II)
Metallonucleases
Sulfonamides
description The bis-(1,10-phenanthroline)copper(I) complex, [Cu(I)(phen)2]+, was the first copper-based artificial nuclease reported in the literature. The biological and ligand-like properties of sulfonamides make them good candidates for fine-tuning the reactivity of the [Cu(phen)2] motif with biomolecules. In this context, we developed three novel copper(II) complexes containing the sulfonamides sulfameter (smtrH) and sulfadimethoxine (sdmxH) and (N^N)-bidentate ligands (2,2′-biyridine or 1,10-phenantroline). The compounds were characterized by chemical and spectroscopic techniques and single-crystal X-ray crystallography. When targeting plasmid DNA, the phen-containing compounds [Cu(smtr−)2(phen)] (1) and [Cu(sdmx−)2(phen)] (2) demonstrated nuclease activity even in the absence of reducing agents. Addition of ascorbic acid resulted in a complete cleavage of DNA by 1 and 2 at concentrations higher than 10 μM. Experiments designed to evaluate the copper intermediates involved in the nuclease effect after reaction with ascorbic acid identified at least the [Cu(I)(N^N)2]+, [Cu(I)(sulfa)(N^N)]+ and [Cu(I)(sulfa)2]+ species. The compounds interact with DNA via groove binding and intercalation as verified by fluorescence spectroscopy, circular dichroism (CD) and molecular docking. The magnitude and preferred mode of binding are dependent on the nature of both N^N ligand and the sulfonamide. The potent nuclease activity of compounds 1 and 2 are well correlated with their antiproliferative and anti-M. tuberculosis profiles. The results presented here demonstrated the potential for further development of copper(II)-sulfonamide-(N^N) complexes as multipurpose metallodrugs.
publishDate 2018
dc.date.none.fl_str_mv 2018-12-11T17:37:54Z
2018-12-11T17:37:54Z
2018-10-01
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.jinorgbio.2018.07.011
Journal of Inorganic Biochemistry, v. 187, p. 85-96.
1873-3344
0162-0134
http://hdl.handle.net/11449/180073
10.1016/j.jinorgbio.2018.07.011
2-s2.0-85050892791
2-s2.0-85050892791.pdf
url http://dx.doi.org/10.1016/j.jinorgbio.2018.07.011
http://hdl.handle.net/11449/180073
identifier_str_mv Journal of Inorganic Biochemistry, v. 187, p. 85-96.
1873-3344
0162-0134
10.1016/j.jinorgbio.2018.07.011
2-s2.0-85050892791
2-s2.0-85050892791.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Inorganic Biochemistry
0,743
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 85-96
application/pdf
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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