In vitro and in silico assessment of antitumor properties and biomolecular binding studies for two new complexes based on Ni II bearing k 2 N,S-donor ligands.

Autor: Farias RL; Univ. Estadual Paulista (Unesp), Instituto de Química, Departamento de Química Analítica, Físico-Química e Inorgânica, Araraquara, Brazil. Electronic address: renan.farias@unesp.br., Polez AMR; Univ. Estadual Paulista (Unesp), Instituto de Química, Departamento de Química Analítica, Físico-Química e Inorgânica, Araraquara, Brazil., Silva DES; Univ. Estadual Paulista (Unesp), Instituto de Química, Departamento de Química Analítica, Físico-Química e Inorgânica, Araraquara, Brazil., Zanetti RD; Univ. Estadual Paulista (Unesp), Instituto de Química, Departamento de Química Analítica, Físico-Química e Inorgânica, Araraquara, Brazil., Moreira MB; Univ. Estadual Paulista (Unesp), Instituto de Química, Departamento de Química Analítica, Físico-Química e Inorgânica, Araraquara, Brazil; Univ. Estadual de Londrina (UEL), Departamento de Química, Londrina, Brazil., Batista VS; Univ. Estadual Paulista (Unesp), Instituto de Química, Laboratório de Química Medicinal, Síntese Orgânica e Modelagem Molecular (LaQMedSOMM), Araraquara, Brazil., Reis BL; Univ. Estadual Paulista (Unesp), Instituto de Química, Laboratório de Química Medicinal, Síntese Orgânica e Modelagem Molecular (LaQMedSOMM), Araraquara, Brazil; Technische Universität Dresden (TUD), Department of Chemistry and Food Chemistry, Dresden, Germany., Nascimento-Júnior NM; Univ. Estadual Paulista (Unesp), Instituto de Química, Laboratório de Química Medicinal, Síntese Orgânica e Modelagem Molecular (LaQMedSOMM), Araraquara, Brazil., Rocha FV; Univ. Federal de São Carlos (UFSCar), Departamento de Química, São Carlos, Brazil., Lima MA; Univ. Federal de São Carlos (UFSCar), Departamento de Química, São Carlos, Brazil., Oliveira AB; Univ. Federal de Sergipe (UFS), Departamento de Química, São Cristóvão, Brazil., Ellena J; Univ. de São Paulo (USP), Instituto de Física de São Carlos, São Carlos, Brazil., Scarim CB; Univ. Estadual Paulista (Unesp), Faculdade de Ciências Farmacêuticas, Araraquara, Brazil., Zambom CR; Univ. Estadual Paulista (Unesp), Instituto de Química, Departamento de Bioquímica e Química Orgânica, Araraquara, Brazil., Brito LD; Univ. Estadual Paulista (Unesp), Instituto de Química, Departamento de Bioquímica e Química Orgânica, Araraquara, Brazil., Garrido SS; Univ. Estadual Paulista (Unesp), Instituto de Química, Departamento de Bioquímica e Química Orgânica, Araraquara, Brazil., Melo APL; Univ. Federal do Rio Grande (FURG), Escola de Química e Alimentos, Rio Grande, Brazil., Bresolin L; Univ. Federal do Rio Grande (FURG), Escola de Química e Alimentos, Rio Grande, Brazil., Tirloni B; Univ. Federal de Santa Maria (UFSM), Departamento de Química, Santa Maria, Brazil., Pereira JCM; Univ. Estadual Paulista (Unesp), Instituto de Química, Departamento de Química Analítica, Físico-Química e Inorgânica, Araraquara, Brazil., Netto AVG; Univ. Estadual Paulista (Unesp), Instituto de Química, Departamento de Química Analítica, Físico-Química e Inorgânica, Araraquara, Brazil.
Jazyk: angličtina
Zdroj: Materials science & engineering. C, Materials for biological applications [Mater Sci Eng C Mater Biol Appl] 2021 Feb; Vol. 121, pp. 111815. Date of Electronic Publication: 2020 Dec 29.
DOI: 10.1016/j.msec.2020.111815
Abstrakt: This work deals with two new molecule-based materials, namely Ni II -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 2 1 /c, also the asymmetric unit comprises of one Ni II ion located on an inversion centre and one anionic ligand, which acts as a κ 2 N,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 IC 50 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 (K b values ~10 4  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 (K b values ⁓10 3  mol L -1 ).
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Databáze: MEDLINE
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