Orthopalladated N,N-dimethyl-1-phenethylamine compounds containing 2,6-lutidine: Synthesis, DNA binding studies and cytotoxicity evaluation
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , , |
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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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 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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 |
|
_version_ |
1808129576055865344 |