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Half sandwich Ru(II)-acylthiourea complexes: DNA/HSA-binding, anti-migration and cell death in a human breast tumor cell line
Dalton Transactions ( IF 4 ) Pub Date : 2017-09-01 00:00:00 , DOI: 10.1039/c7dt01801k
Legna Colina-Vegas 1, 2, 3 , Liany Luna-Dulcey 2, 3, 4 , Ana M. Plutín 5, 6, 7 , Eduardo E. Castellano 3, 8, 9 , Marcia R. Cominetti 2, 3, 4 , Alzir A. Batista 1, 2, 3
Affiliation  

Organometallic ruthenium complexes as potential anticancer agents have been explored due to their suitable properties, such as stability in the solid state and in solution, water solubility and low toxicity. In this study, eight metal complexes of this class were synthesized, characterized and their important biological activities against a human breast tumor cell line (MDA-MB-231) were studied. Complexes 1–8 were obtained in good yields and have been characterized by satisfactory elemental analyses, IR, 1D and 2D 1H and 13C{1H} NMR, UV-Vis spectroscopy, cyclic voltammetry, ESI-MS and X-ray diffractometry (1, 2, 3 and 6). All complexes exhibit growth inhibition on human breast and lung tumor cell lines, with IC50 values ranging from 6.0 to 45.0 μM in 48 h. Four compounds were selected to evaluate the changes in the morphology, clonogenic, migration, cell cycle arrest and cell death in MDA-MB-231 cells. The complexes are able to induce morphological changes and inhibit the size, number of colonies and cell migration, and induce cell cycle arrest in the sub-G1 phase and apoptosis cell death. The interaction of the complexes with DNA was determined by performing spectroscopic titration, a competitive assay with thiazole orange, circular dichroism, gel electrophoresis and interactions with guanosine or guanosine monophosphate by 1H NMR, indicating the non-covalent interaction. The HSA binding affinity measured by spectrophotometric titration, revealed the hydrophobic and spontaneous association with the human protein. Overall, the studies indicated that these metal complexes are potential agents against MDA-MB-231 cells, encouraging us to continue studies of these types of compounds.

中文翻译:

半夹心Ru(II)-酰基硫脲复合物:人乳腺肿瘤细胞系中的DNA / HSA结合,抗迁移和细胞死亡

由于其合适的性质,例如在固态和溶液中的稳定性,水溶性和低毒性,已经探索了有机金属钌配合物作为潜在的抗癌剂。在该研究中,合成,表征了八种此类金属络合物,并研究了它们对人乳腺肿瘤细胞系(MDA-MB-231)的重要生物学活性。配合物1–8以良好的产率获得,并具有令人满意的元素分析,IR,1D和2D 1 H和13 C { 1 H} NMR,UV-Vis光谱,循环伏安法,ESI-MS和X射线衍射法表征(1236)。所有复合物在人乳腺和肺部肿瘤细胞系上均表现出生长抑制作用,在48小时内IC 50值范围为6.0至45.0μM。选择了四种化合物来评估MDA-MB-231细胞的形态,克隆形成,迁移,细胞周期停滞和细胞死亡的变化。该复合物能够诱导形态变化并抑制大小,菌落数量和细胞迁移,并诱导亚G1期细胞周期停滞和凋亡细胞死亡。与DNA的复合物的相互作用是通过用鸟苷或鸟苷酸进行分光滴定,竞争性测定用噻唑橙,圆二色性,凝胶电泳和相互作用确定11 H NMR,表明非共价相互作用。通过分光光度滴定法测量的HSA结合亲和力显示了与人蛋白质的疏水性和自发性缔合。总体而言,研究表明这些金属络合物是抗MDA-MB-231细胞的潜在药物,这鼓励我们继续研究这些类型的化合物。
更新日期:2017-09-18
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