Gold(III) heteroleptic complexes with SNS-thiosemicarbazonate ligands as cytotoxic agents: Experimental and computational insights into the mechanism of action

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dc.contributor.authorKaiser da Silva, Amandha
dc.contributor.authorMateus Santos, Malú
dc.contributor.authorAparecida Candido, Pâmela
dc.contributor.authorde Oliveira Lopes, Érica [UNESP]
dc.contributor.authorRogério Pavan, Fernando [UNESP]
dc.contributor.authorAparecida Carneiro, Zumira
dc.contributor.authorVinícius da Silva, Marcos
dc.contributor.authorJosé Freire de Oliveira, Carlo
dc.contributor.authorAzevedo Batista, Alzir
dc.contributor.authorJunio de Oliveira, Ronaldo
dc.contributor.authorMarcelo Deflon, Victor
dc.contributor.authorIvo da Silva Maia, Pedro
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionAvenida Getúlio Guaritá
dc.contributor.institutionUniversidade Federal do Triângulo Mineiro
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversidade Federal de São Carlos (UFSCar)
dc.date.accessioned2022-04-29T08:46:42Z
dc.date.available2022-04-29T08:46:42Z
dc.date.issued2022-06-01
dc.description.abstractNew 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.en
dc.description.affiliationInstituto de Química de São Carlos Universidade de São Paulo, Av. Trabalhador São Carlense, 400, SP
dc.description.affiliationDepartamento de Microbiologia Imunologia e Parasitologia Universidade Federal do Triângulo Mineiro Avenida Getúlio Guaritá, Minas Gerais
dc.description.affiliationNúcleo de Desenvolvimento de Compostos Bioativos (NDCBio) Universidade Federal do Triângulo Mineiro, Av. Dr. Randolfo Borges 1400, MG
dc.description.affiliationFaculdade de Ciências Farmacêuticas Universidade Estadual Paulista, SP
dc.description.affiliationDepartamento de Análises Clínicas Toxicológicas e Bromatológicas Faculdade de Ciências Farmacêuticas de Ribeirão Preto FCFRP-USP Universidade de São Paulo, Avenida do Café s/n, SP
dc.description.affiliationDepartamento de Química Universidade Federal de São Carlos, SP
dc.description.affiliationUnespFaculdade de Ciências Farmacêuticas Universidade Estadual Paulista, SP
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdCNPq: 309145/2020-1
dc.description.sponsorshipIdCNPq: 312328/2019-2
dc.description.sponsorshipIdCNPq: 424095/2018-1
dc.description.sponsorshipIdCNPq: 438316/2018-5
dc.identifierhttp://dx.doi.org/10.1016/j.poly.2022.115767
dc.identifier.citationPolyhedron, v. 219.
dc.identifier.doi10.1016/j.poly.2022.115767
dc.identifier.issn0277-5387
dc.identifier.scopus2-s2.0-85126856953
dc.identifier.urihttp://hdl.handle.net/11449/231638
dc.language.isoeng
dc.relation.ispartofPolyhedron
dc.sourceScopus
dc.subjectDNA
dc.subjectDocking
dc.subjectGold complexes
dc.subjectHuman serum albumin
dc.subjectThioredoxin reductase
dc.subjectThiosemicarbazones
dc.titleGold(III) heteroleptic complexes with SNS-thiosemicarbazonate ligands as cytotoxic agents: Experimental and computational insights into the mechanism of actionen
dc.typeArtigo
unesp.departmentPrincípios Ativos Naturais e Toxicologia - FCFpt

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Araraquara - FCF - Faculdade de Ciências Farmacêuticas