Gold(III) heteroleptic complexes with SNS-thiosemicarbazonate ligands as cytotoxic agents: Experimental and computational insights into the mechanism of action
Autor(a) principal: | |
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Data de Publicação: | 2022 |
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.2022.115767 http://hdl.handle.net/11449/231638 |
Resumo: | New gold(III) heteroleptic complexes of general formula [AuX(dmtsc)], with (dmtsc)2– = (diethylaminothiocarbonyl)benzimidoyl-morpholinyl-thiosemicarbazonate and X = xant– (ethyl xanthate) or damp– (dimethyl-1-phenylmethanamine), were synthesized and compared to the chlorido precursor [AuCl(dmtsc)]. The characterization of the new complexes included FTIR, elemental analysis, molar conductivity, UV–Vis, 1H and 13C NMR spectroscopies and ESI(+)-MS. In addition, the xanthate derivative was analyzed by single-crystal X-ray diffraction. In vitro assays against three tumor cell lines (B16-F10, HCT-8 and MDA-MB-231) showed that the gold(III) complexes display remarkable antiproliferative effects on human breast adenocarcinoma cell line with influence of the co-ligands. The cytotoxicity on VERO cells was also investigated revealing that the organometallic complex [Au(damp)(dmtsc)] was the most selective compound for MDA-MB-231, although not the most active. Attempting to comprehend their behavior in biological medium, studies involving the interactions with possible biological targets were performed by experimental methods and theoretical docking simulations. Their results indicated that HSA might be a probable carrier of the compounds in the biological medium, whereas DNA is not supposed to be their main target. On the other hand, all compounds totally inhibited thioredoxin reductase enzyme (TrxR) at the concentration of 50 μM and formed significant molecular interactions, suggesting that it might be one of the molecular targets of these gold(III) complexes. |
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Gold(III) heteroleptic complexes with SNS-thiosemicarbazonate ligands as cytotoxic agents: Experimental and computational insights into the mechanism of actionDNADockingGold complexesHuman serum albuminThioredoxin reductaseThiosemicarbazonesNew gold(III) heteroleptic complexes of general formula [AuX(dmtsc)], with (dmtsc)2– = (diethylaminothiocarbonyl)benzimidoyl-morpholinyl-thiosemicarbazonate and X = xant– (ethyl xanthate) or damp– (dimethyl-1-phenylmethanamine), were synthesized and compared to the chlorido precursor [AuCl(dmtsc)]. The characterization of the new complexes included FTIR, elemental analysis, molar conductivity, UV–Vis, 1H and 13C NMR spectroscopies and ESI(+)-MS. In addition, the xanthate derivative was analyzed by single-crystal X-ray diffraction. In vitro assays against three tumor cell lines (B16-F10, HCT-8 and MDA-MB-231) showed that the gold(III) complexes display remarkable antiproliferative effects on human breast adenocarcinoma cell line with influence of the co-ligands. The cytotoxicity on VERO cells was also investigated revealing that the organometallic complex [Au(damp)(dmtsc)] was the most selective compound for MDA-MB-231, although not the most active. Attempting to comprehend their behavior in biological medium, studies involving the interactions with possible biological targets were performed by experimental methods and theoretical docking simulations. Their results indicated that HSA might be a probable carrier of the compounds in the biological medium, whereas DNA is not supposed to be their main target. On the other hand, all compounds totally inhibited thioredoxin reductase enzyme (TrxR) at the concentration of 50 μM and formed significant molecular interactions, suggesting that it might be one of the molecular targets of these gold(III) complexes.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Instituto de Química de São Carlos Universidade de São Paulo, Av. Trabalhador São Carlense, 400, SPDepartamento de Microbiologia Imunologia e Parasitologia Universidade Federal do Triângulo Mineiro Avenida Getúlio Guaritá, Minas GeraisNúcleo de Desenvolvimento de Compostos Bioativos (NDCBio) Universidade Federal do Triângulo Mineiro, Av. Dr. Randolfo Borges 1400, MGFaculdade de Ciências Farmacêuticas Universidade Estadual Paulista, SPDepartamento de Análises Clínicas Toxicológicas e Bromatológicas Faculdade de Ciências Farmacêuticas de Ribeirão Preto FCFRP-USP Universidade de São Paulo, Avenida do Café s/n, SPDepartamento de Química Universidade Federal de São Carlos, SPFaculdade de Ciências Farmacêuticas Universidade Estadual Paulista, SPCNPq: 309145/2020-1CNPq: 312328/2019-2CNPq: 424095/2018-1CNPq: 438316/2018-5Universidade de São Paulo (USP)Avenida Getúlio GuaritáUniversidade Federal do Triângulo MineiroUniversidade Estadual Paulista (UNESP)Universidade Federal de São Carlos (UFSCar)Kaiser da Silva, AmandhaMateus Santos, MalúAparecida Candido, Pâmelade Oliveira Lopes, Érica [UNESP]Rogério Pavan, Fernando [UNESP]Aparecida Carneiro, ZumiraVinícius da Silva, MarcosJosé Freire de Oliveira, CarloAzevedo Batista, AlzirJunio de Oliveira, RonaldoMarcelo Deflon, VictorIvo da Silva Maia, Pedro2022-04-29T08:46:42Z2022-04-29T08:46:42Z2022-06-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.poly.2022.115767Polyhedron, v. 219.0277-5387http://hdl.handle.net/11449/23163810.1016/j.poly.2022.1157672-s2.0-85126856953Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPolyhedroninfo:eu-repo/semantics/openAccess2024-06-24T14:51:41Zoai:repositorio.unesp.br:11449/231638Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T18:01:21.094603Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Gold(III) heteroleptic complexes with SNS-thiosemicarbazonate ligands as cytotoxic agents: Experimental and computational insights into the mechanism of action |
title |
Gold(III) heteroleptic complexes with SNS-thiosemicarbazonate ligands as cytotoxic agents: Experimental and computational insights into the mechanism of action |
spellingShingle |
Gold(III) heteroleptic complexes with SNS-thiosemicarbazonate ligands as cytotoxic agents: Experimental and computational insights into the mechanism of action Kaiser da Silva, Amandha DNA Docking Gold complexes Human serum albumin Thioredoxin reductase Thiosemicarbazones |
title_short |
Gold(III) heteroleptic complexes with SNS-thiosemicarbazonate ligands as cytotoxic agents: Experimental and computational insights into the mechanism of action |
title_full |
Gold(III) heteroleptic complexes with SNS-thiosemicarbazonate ligands as cytotoxic agents: Experimental and computational insights into the mechanism of action |
title_fullStr |
Gold(III) heteroleptic complexes with SNS-thiosemicarbazonate ligands as cytotoxic agents: Experimental and computational insights into the mechanism of action |
title_full_unstemmed |
Gold(III) heteroleptic complexes with SNS-thiosemicarbazonate ligands as cytotoxic agents: Experimental and computational insights into the mechanism of action |
title_sort |
Gold(III) heteroleptic complexes with SNS-thiosemicarbazonate ligands as cytotoxic agents: Experimental and computational insights into the mechanism of action |
author |
Kaiser da Silva, Amandha |
author_facet |
Kaiser da Silva, Amandha Mateus Santos, Malú Aparecida Candido, Pâmela de Oliveira Lopes, Érica [UNESP] Rogério Pavan, Fernando [UNESP] Aparecida Carneiro, Zumira Vinícius da Silva, Marcos José Freire de Oliveira, Carlo Azevedo Batista, Alzir Junio de Oliveira, Ronaldo Marcelo Deflon, Victor Ivo da Silva Maia, Pedro |
author_role |
author |
author2 |
Mateus Santos, Malú Aparecida Candido, Pâmela de Oliveira Lopes, Érica [UNESP] Rogério Pavan, Fernando [UNESP] Aparecida Carneiro, Zumira Vinícius da Silva, Marcos José Freire de Oliveira, Carlo Azevedo Batista, Alzir Junio de Oliveira, Ronaldo Marcelo Deflon, Victor Ivo da Silva Maia, Pedro |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Avenida Getúlio Guaritá Universidade Federal do Triângulo Mineiro Universidade Estadual Paulista (UNESP) Universidade Federal de São Carlos (UFSCar) |
dc.contributor.author.fl_str_mv |
Kaiser da Silva, Amandha Mateus Santos, Malú Aparecida Candido, Pâmela de Oliveira Lopes, Érica [UNESP] Rogério Pavan, Fernando [UNESP] Aparecida Carneiro, Zumira Vinícius da Silva, Marcos José Freire de Oliveira, Carlo Azevedo Batista, Alzir Junio de Oliveira, Ronaldo Marcelo Deflon, Victor Ivo da Silva Maia, Pedro |
dc.subject.por.fl_str_mv |
DNA Docking Gold complexes Human serum albumin Thioredoxin reductase Thiosemicarbazones |
topic |
DNA Docking Gold complexes Human serum albumin Thioredoxin reductase Thiosemicarbazones |
description |
New gold(III) heteroleptic complexes of general formula [AuX(dmtsc)], with (dmtsc)2– = (diethylaminothiocarbonyl)benzimidoyl-morpholinyl-thiosemicarbazonate and X = xant– (ethyl xanthate) or damp– (dimethyl-1-phenylmethanamine), were synthesized and compared to the chlorido precursor [AuCl(dmtsc)]. The characterization of the new complexes included FTIR, elemental analysis, molar conductivity, UV–Vis, 1H and 13C NMR spectroscopies and ESI(+)-MS. In addition, the xanthate derivative was analyzed by single-crystal X-ray diffraction. In vitro assays against three tumor cell lines (B16-F10, HCT-8 and MDA-MB-231) showed that the gold(III) complexes display remarkable antiproliferative effects on human breast adenocarcinoma cell line with influence of the co-ligands. The cytotoxicity on VERO cells was also investigated revealing that the organometallic complex [Au(damp)(dmtsc)] was the most selective compound for MDA-MB-231, although not the most active. Attempting to comprehend their behavior in biological medium, studies involving the interactions with possible biological targets were performed by experimental methods and theoretical docking simulations. Their results indicated that HSA might be a probable carrier of the compounds in the biological medium, whereas DNA is not supposed to be their main target. On the other hand, all compounds totally inhibited thioredoxin reductase enzyme (TrxR) at the concentration of 50 μM and formed significant molecular interactions, suggesting that it might be one of the molecular targets of these gold(III) complexes. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-04-29T08:46:42Z 2022-04-29T08:46:42Z 2022-06-01 |
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.2022.115767 Polyhedron, v. 219. 0277-5387 http://hdl.handle.net/11449/231638 10.1016/j.poly.2022.115767 2-s2.0-85126856953 |
url |
http://dx.doi.org/10.1016/j.poly.2022.115767 http://hdl.handle.net/11449/231638 |
identifier_str_mv |
Polyhedron, v. 219. 0277-5387 10.1016/j.poly.2022.115767 2-s2.0-85126856953 |
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 |
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1808128885965979648 |