Orthopalladated N,N-dimethyl-1-phenethylamine compounds containing 2,6-lutidine: Synthesis, DNA binding studies and cytotoxicity evaluation

Detalhes bibliográficos
Autor(a) principal: Zanetti, Renan D. [UNESP]
Data de Publicação: 2023
Outros Autores: da Cunha, Gislaine A. [UNESP], Moreira, Mariete B., Farias, Renan L., de Souza, Ronan F.F., de Godoy, Paulo R.D.V., Brassesco, María Sol, Rocha, Fillipe V., Lima, Mauro A., Mauro, Antonio E. [UNESP], Netto, Adelino V.G. [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.poly.2022.116185
http://hdl.handle.net/11449/247900
Resumo: Metathetical reactions involving [Pd(C2,N-dmpa)(μ-Cl)]2 (1) and the appropriate halides/pseudohalides salts afforded cyclopalladated dimers of the type [Pd(C2,N-dmpa)(μ-X)]2 (dmpa = S(−) enantiomer of N,N-dimethyl-1-phenethylamine; {X = Cl (1) and N3 (2)}. Mononuclear compounds of general formulae [Pd(C2,N-dmpa)(X)(lut)] {X = Cl (1a) and N3 (2a)} were obtained by bridge-splitting reactions involving the corresponding [Pd(C2,N-dmpa)(μ-X)]2 with 2,6-lutidine (lut) in the 1:2 M ratio at room temperature. Both the cyclopalladated compounds were characterized by means of elemental analysis, FT-IR, Raman, 1H and 13C NMR spectroscopy. The antiproliferative activity of the mononuclear compounds 1a-2a was evaluated towards human glioblastoma (U251 and T98G) and melanoma cell lines (HT144 and LB373) and their IC50 values determined between 1 and 6 μM. In most cases, the cytotoxic effects of compounds 1a-2a showed to be similar to those of cisplatin (depending on the cell line), what is of utmost importance when considering treatment alternatives for these aggressive tumor types. Binding studies on the representative compound 2a towards ct-DNA, however, showed low or no affinity, suggesting that the observed cytotoxicity against the human cell lines may involve different mechanisms of action compared to that of the platinum-based chemotherapy drug. The ability of 1a to induce the inhibition of topoisomerase IIα activity has also been investigated. These cyclopalladated compounds can be transported and distributed through the body by human serum albumin (HSA), as observed by competition and computational studies with the protein. These findings are very promising and have motivated further studies for the design of new and bioactive cyclopalladated compounds for future medicinal purposes.
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spelling Orthopalladated N,N-dimethyl-1-phenethylamine compounds containing 2,6-lutidine: Synthesis, DNA binding studies and cytotoxicity evaluationAlbuminCyclopalladated complexCytotoxicityDNAN,N-Dimethyl-1-phenethylamineMetathetical reactions involving [Pd(C2,N-dmpa)(μ-Cl)]2 (1) and the appropriate halides/pseudohalides salts afforded cyclopalladated dimers of the type [Pd(C2,N-dmpa)(μ-X)]2 (dmpa = S(−) enantiomer of N,N-dimethyl-1-phenethylamine; {X = Cl (1) and N3 (2)}. Mononuclear compounds of general formulae [Pd(C2,N-dmpa)(X)(lut)] {X = Cl (1a) and N3 (2a)} were obtained by bridge-splitting reactions involving the corresponding [Pd(C2,N-dmpa)(μ-X)]2 with 2,6-lutidine (lut) in the 1:2 M ratio at room temperature. Both the cyclopalladated compounds were characterized by means of elemental analysis, FT-IR, Raman, 1H and 13C NMR spectroscopy. The antiproliferative activity of the mononuclear compounds 1a-2a was evaluated towards human glioblastoma (U251 and T98G) and melanoma cell lines (HT144 and LB373) and their IC50 values determined between 1 and 6 μM. In most cases, the cytotoxic effects of compounds 1a-2a showed to be similar to those of cisplatin (depending on the cell line), what is of utmost importance when considering treatment alternatives for these aggressive tumor types. Binding studies on the representative compound 2a towards ct-DNA, however, showed low or no affinity, suggesting that the observed cytotoxicity against the human cell lines may involve different mechanisms of action compared to that of the platinum-based chemotherapy drug. The ability of 1a to induce the inhibition of topoisomerase IIα activity has also been investigated. These cyclopalladated compounds can be transported and distributed through the body by human serum albumin (HSA), as observed by competition and computational studies with the protein. These findings are very promising and have motivated further studies for the design of new and bioactive cyclopalladated compounds for future medicinal purposes.Departamento de Química Analítica Físico-Química e Inorgânica Instituto de Química Univ Estadual Paulista – UNESP, P.O. Box 355, SPDepartamento de Química Univ Estadual de Maringá – UEM, PRDepartamento de Química Pontifícia Universidade Católica do Rio de Janeiro - PUC-Rio, RJCentro de Engenharia e Ciências Exatas (CECE) Univ Estadual do Oeste de Paraná – UNIOESTE, PRDepartamento de Biologia Faculdade de Filosofia Ciências e Letras de Ribeirão Preto – USP, 14040-901, SPCentro de Ciências Exatas e de Tecnologia - CCET Universidade Federal de São Carlos – UFSCar, SPDepartamento de Química Analítica Físico-Química e Inorgânica Instituto de Química Univ Estadual Paulista – UNESP, P.O. Box 355, SPUniversidade Estadual Paulista (UNESP)Universidade Estadual de Maringá (UEM)Pontifícia Universidade Católica do Rio de Janeiro - PUC-RioUniv Estadual do Oeste de Paraná – UNIOESTEUniversidade de São Paulo (USP)Universidade Federal de São Carlos (UFSCar)Zanetti, Renan D. [UNESP]da Cunha, Gislaine A. [UNESP]Moreira, Mariete B.Farias, Renan L.de Souza, Ronan F.F.de Godoy, Paulo R.D.V.Brassesco, María SolRocha, Fillipe V.Lima, Mauro A.Mauro, Antonio E. [UNESP]Netto, Adelino V.G. [UNESP]2023-07-29T13:29:02Z2023-07-29T13:29:02Z2023-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.poly.2022.116185Polyhedron, v. 229.0277-5387http://hdl.handle.net/11449/24790010.1016/j.poly.2022.1161852-s2.0-85142123278Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPolyhedroninfo:eu-repo/semantics/openAccess2023-07-29T13:29:02Zoai:repositorio.unesp.br:11449/247900Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-06T00:02:29.357533Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Orthopalladated N,N-dimethyl-1-phenethylamine compounds containing 2,6-lutidine: Synthesis, DNA binding studies and cytotoxicity evaluation
title Orthopalladated N,N-dimethyl-1-phenethylamine compounds containing 2,6-lutidine: Synthesis, DNA binding studies and cytotoxicity evaluation
spellingShingle Orthopalladated N,N-dimethyl-1-phenethylamine compounds containing 2,6-lutidine: Synthesis, DNA binding studies and cytotoxicity evaluation
Zanetti, Renan D. [UNESP]
Albumin
Cyclopalladated complex
Cytotoxicity
DNA
N,N-Dimethyl-1-phenethylamine
title_short Orthopalladated N,N-dimethyl-1-phenethylamine compounds containing 2,6-lutidine: Synthesis, DNA binding studies and cytotoxicity evaluation
title_full Orthopalladated N,N-dimethyl-1-phenethylamine compounds containing 2,6-lutidine: Synthesis, DNA binding studies and cytotoxicity evaluation
title_fullStr Orthopalladated N,N-dimethyl-1-phenethylamine compounds containing 2,6-lutidine: Synthesis, DNA binding studies and cytotoxicity evaluation
title_full_unstemmed Orthopalladated N,N-dimethyl-1-phenethylamine compounds containing 2,6-lutidine: Synthesis, DNA binding studies and cytotoxicity evaluation
title_sort Orthopalladated N,N-dimethyl-1-phenethylamine compounds containing 2,6-lutidine: Synthesis, DNA binding studies and cytotoxicity evaluation
author Zanetti, Renan D. [UNESP]
author_facet Zanetti, Renan D. [UNESP]
da Cunha, Gislaine A. [UNESP]
Moreira, Mariete B.
Farias, Renan L.
de Souza, Ronan F.F.
de Godoy, Paulo R.D.V.
Brassesco, María Sol
Rocha, Fillipe V.
Lima, Mauro A.
Mauro, Antonio E. [UNESP]
Netto, Adelino V.G. [UNESP]
author_role author
author2 da Cunha, Gislaine A. [UNESP]
Moreira, Mariete B.
Farias, Renan L.
de Souza, Ronan F.F.
de Godoy, Paulo R.D.V.
Brassesco, María Sol
Rocha, Fillipe V.
Lima, Mauro A.
Mauro, Antonio E. [UNESP]
Netto, Adelino V.G. [UNESP]
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
Universidade Estadual de Maringá (UEM)
Pontifícia Universidade Católica do Rio de Janeiro - PUC-Rio
Univ Estadual do Oeste de Paraná – UNIOESTE
Universidade de São Paulo (USP)
Universidade Federal de São Carlos (UFSCar)
dc.contributor.author.fl_str_mv Zanetti, Renan D. [UNESP]
da Cunha, Gislaine A. [UNESP]
Moreira, Mariete B.
Farias, Renan L.
de Souza, Ronan F.F.
de Godoy, Paulo R.D.V.
Brassesco, María Sol
Rocha, Fillipe V.
Lima, Mauro A.
Mauro, Antonio E. [UNESP]
Netto, Adelino V.G. [UNESP]
dc.subject.por.fl_str_mv Albumin
Cyclopalladated complex
Cytotoxicity
DNA
N,N-Dimethyl-1-phenethylamine
topic Albumin
Cyclopalladated complex
Cytotoxicity
DNA
N,N-Dimethyl-1-phenethylamine
description Metathetical reactions involving [Pd(C2,N-dmpa)(μ-Cl)]2 (1) and the appropriate halides/pseudohalides salts afforded cyclopalladated dimers of the type [Pd(C2,N-dmpa)(μ-X)]2 (dmpa = S(−) enantiomer of N,N-dimethyl-1-phenethylamine; {X = Cl (1) and N3 (2)}. Mononuclear compounds of general formulae [Pd(C2,N-dmpa)(X)(lut)] {X = Cl (1a) and N3 (2a)} were obtained by bridge-splitting reactions involving the corresponding [Pd(C2,N-dmpa)(μ-X)]2 with 2,6-lutidine (lut) in the 1:2 M ratio at room temperature. Both the cyclopalladated compounds were characterized by means of elemental analysis, FT-IR, Raman, 1H and 13C NMR spectroscopy. The antiproliferative activity of the mononuclear compounds 1a-2a was evaluated towards human glioblastoma (U251 and T98G) and melanoma cell lines (HT144 and LB373) and their IC50 values determined between 1 and 6 μM. In most cases, the cytotoxic effects of compounds 1a-2a showed to be similar to those of cisplatin (depending on the cell line), what is of utmost importance when considering treatment alternatives for these aggressive tumor types. Binding studies on the representative compound 2a towards ct-DNA, however, showed low or no affinity, suggesting that the observed cytotoxicity against the human cell lines may involve different mechanisms of action compared to that of the platinum-based chemotherapy drug. The ability of 1a to induce the inhibition of topoisomerase IIα activity has also been investigated. These cyclopalladated compounds can be transported and distributed through the body by human serum albumin (HSA), as observed by competition and computational studies with the protein. These findings are very promising and have motivated further studies for the design of new and bioactive cyclopalladated compounds for future medicinal purposes.
publishDate 2023
dc.date.none.fl_str_mv 2023-07-29T13:29:02Z
2023-07-29T13:29:02Z
2023-01-01
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.poly.2022.116185
Polyhedron, v. 229.
0277-5387
http://hdl.handle.net/11449/247900
10.1016/j.poly.2022.116185
2-s2.0-85142123278
url http://dx.doi.org/10.1016/j.poly.2022.116185
http://hdl.handle.net/11449/247900
identifier_str_mv Polyhedron, v. 229.
0277-5387
10.1016/j.poly.2022.116185
2-s2.0-85142123278
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Polyhedron
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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)
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