Farias R L, Polez A M R, Silva D E S, Zanetti R D, Moreira M B, Batista V S, Reis B L, Nascimento-Júnior N M, Rocha F V, Lima M A, Oliveira A B, Ellena J, Scarim C B, Zambom C R, Brito L D, Garrido S S, Melo A P L, Bresolin L, Tirloni B, Pereira J C M, Netto A V G
Univ. Estadual Paulista (Unesp), Instituto de Química, Departamento de Química Analítica, Físico-Química e Inorgânica, Araraquara, Brazil.
Univ. Estadual Paulista (Unesp), Instituto de Química, Departamento de Química Analítica, Físico-Química e Inorgânica, Araraquara, Brazil.
Mater Sci Eng C Mater Biol Appl. 2021 Feb;121:111815. doi: 10.1016/j.msec.2020.111815. Epub 2020 Dec 29.
This work deals with two new molecule-based materials, namely Ni-complexes of general formulae [Ni(L1)] (Ni1) and [Ni(L2)] (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/c, also the asymmetric unit comprises of one Ni ion located on an inversion centre and one anionic ligand, which acts as a κN,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 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 values ~10 mol L) 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 values ⁓10 mol L).
这项工作涉及两种新型分子基材料，即通式为[Ni(L1)]（Ni1）和[Ni(L2)]（Ni2）的镍配合物，其中L1 = 反式肉桂醛 - N(4)-甲基硫代氨基脲，L2 = 反式肉桂醛 - N(4)-乙基硫代氨基脲，作为潜在的抗肿瘤剂。两种化合物均通过元素分析、摩尔电导率和光谱技术（傅里叶变换红外光谱和核磁共振）进行了表征。它们的分子结构通过单晶X射线衍射分析获得。每一种都结晶于单斜空间群P 2/c，不对称单元包含位于对称中心的一个镍离子和一个阴离子配体，该配体作为κN,S供体形成一个五元金属环。通过MTT法对两种选定的肿瘤细胞系（MCF-7和A549）和非肿瘤成纤维细胞系（MRC-5）对这些化合物进行了筛选。在两种肿瘤细胞中，所有化合物均表现出比对照药物（顺铂）更高的细胞毒性。MCF-7和A549的IC值范围分别为3.70 - 41.37 μM和1.06 - 14.91 μM。重要的是，它们在MRC-5中的毒性均低于顺铂，SI值范围为11.80 - 86.60。红细胞（RBC）试验表明Ni2无毒，因为其溶血作用降低（在1 - 10 μM时为0 - 9%）。通过分光光度吸收和发射滴定、电泳和圆二色性实验相结合的方法研究了DNA结合情况。结果，这些金属配合物不能与DNA强烈结合（K值约为10 mol L），但表明存在沟槽结合相互作用。在这项工作中还评估了它们对2,2-二苯基-1-苦基肼（DPPH）自由基的清除能力，但未检测到重要的抗氧化行为。此外，通过色氨酸发射猝灭、华法林竞争试验和分子对接方案研究了Ni1和Ni2与人血清白蛋白（HSA）的相互作用。HSA结合分析表明两种配合物对Sudlow位点I具有良好的亲和力（K值约为10 mol L）。
