In vitro and in silico assessment of antitumor properties and biomolecular binding studies for two new complexes based on NiII bearing k2N,S-donor ligands
| Autor: | A.M.R. Polez, Fillipe V. Rocha, Mauro A. Lima, Bárbara Tirloni, Renan D. Zanetti, Victor S. Batista, Carolina Reis Zambom, Leandro Bresolin, José Clayston Melo Pereira, Mariete Barbosa Moreira, B.L. Reis, Adriano Bof de Oliveira, Javier Ellena, Adelino Vieira de Godoy Netto, Saulo Santesso Garrido, Renan Lira de Farias, Débora E.S. Silva, L.D. Brito, Cauê Benito Scarim, Nailton M. Nascimento-Júnior, A.P.L. Melo |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp), Univ. Estadual de Londrina (UEL), Technische Universität Dresden (TUD), Universidade Federal de São Carlos (UFSCar), Universidade Federal de Sergipe (UFS), Universidade de São Paulo (USP), Escola de Química e Alimentos |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Circular dichroism
Materials science Metallodrugs Stereochemistry Molar conductivity Bioengineering Nickel(II)-complexes 02 engineering and technology 010402 general chemistry 01 natural sciences Biomaterials chemistry.chemical_compound medicine Molecule Semicarbazone Quenching (fluorescence) CITOTOXINAS Ligand Tryptophan Protein-ligand binding studies 021001 nanoscience & nanotechnology Human serum albumin 0104 chemical sciences N S-donor ligands mMolecular docking chemistry Mechanics of Materials 0210 nano-technology medicine.drug |
| Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Made available in DSpace on 2021-06-25T10:48:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-02-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) This work deals with two new molecule-based materials, namely NiII-complexes of general formulae [Ni(L1)2] (Ni1) and [Ni(L2)2] (Ni2), where L1 = trans-cinnamaldehyde-N(4)-methyl thiosemicarbazone and L2 = trans-cinnamaldehyde-N(4)-ethyl thiosemicarbazone, as potential antitumor agents. Both compounds were characterized by elemental analysis, molar conductivity and spectroscopic techniques (FTIR and NMR). Their molecular structures were obtained by single-crystal X-ray diffraction analysis. Each one crystallizes in a monoclinic space group P 21/c, also the asymmetric unit comprises of one NiII ion located on an inversion centre and one anionic ligand, which acts as a κ2N,S-donor affording a five-membered metallaring. The compounds were screened against two selected tumour cell lines (MCF-7 and A549) and non-tumour fibroblasts cell line (MRC-5) via MTT assays. In both tumour cells, all compounds exhibited higher cytotoxicity than the control drug (cisplatin). The IC50 values ranges of 3.70 – 41.37 μM and 1.06 – 14.91 μM were found for MCF-7 and A549, respectively. Importantly, all of them were less toxicity than cisplatin in MRC-5 with SI values ranged at 11.80 – 86.60. The red blood cell (RBC) assay revealed Ni2 as non-toxic due to its reduced haemolytic effect (0‐–9% at 1‐–10 μM). The DNA binding was investigated through a combination of spectrophotometric absorption and emission titrations, electrophoresis, and circular dichroism experiments. As a result, these metal complexes were not able to strongly binding to DNA (Kb values ~104 mol L‐−1) but suggesting groove-binding interactions. The scavenging ability of them towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical was also evaluated in this work, but no important antioxidant behaviour was detected. Further, the interaction of Ni1 and Ni2 to human serum albumin (HSA) was explored by quenching of tryptophan emission, warfarin competitive assay, and molecular docking protocols. The HSA binding analyses indicated good affinity of both complexes to Sudlow site I (Kb values ⁓103 mol L−1). Univ. Estadual Paulista (Unesp) Instituto de Química Departamento de Química Analítica Físico-Química e Inorgânica Univ. Estadual de Londrina (UEL) Departamento de Química Univ. Estadual Paulista (Unesp) Instituto de Química Laboratório de Química Medicinal Síntese Orgânica e Modelagem Molecular (LaQMedSOMM) Technische Universität Dresden (TUD) Department of Chemistry and Food Chemistry Univ. Federal de São Carlos (UFSCar) Departamento de Química Univ. Federal de Sergipe (UFS) Departamento de Química Univ. de São Paulo (USP) Instituto de Física de São Carlos Univ. Estadual Paulista (Unesp) Faculdade de Ciências Farmacêuticas Univ. Estadual Paulista (Unesp) Instituto de Química Departamento de Bioquímica e Química Orgânica Univ. Federal do Rio Grande (FURG) Escola de Química e Alimentos Univ. Federal de Santa Maria (UFSM) Departamento de Química Univ. Estadual Paulista (Unesp) Instituto de Química Departamento de Química Analítica Físico-Química e Inorgânica Univ. Estadual Paulista (Unesp) Instituto de Química Laboratório de Química Medicinal Síntese Orgânica e Modelagem Molecular (LaQMedSOMM) Univ. Estadual Paulista (Unesp) Faculdade de Ciências Farmacêuticas Univ. Estadual Paulista (Unesp) Instituto de Química Departamento de Bioquímica e Química Orgânica CAPES: 001 FAPESP: 15/12098-0 FAPESP: 2016/17711-5 CNPq: 305190/2017-2 CNPq: 422105/2016-3 |
| Databáze: | OpenAIRE |
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