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含生物活性配体的低维化合物。第十四部分:三(5-氯-8-喹啉醇)合镓(III)配合物对人癌细胞系的高选择性抗增殖活性。

Low-dimensional compounds containing bioactive ligands. Part XIV: High selective antiproliferative activity of tris(5-chloro-8-quinolinolato)gallium(III) complex against human cancer cell lines.

机构信息

Department of Inorganic Chemistry, Institute of Chemistry, P. J. Šafárik University in Košice, Moyzesova 11, 040 01 Košice, Slovakia.

Department of Biophysics, Faculty of Science, Palacký University, Šlechtitelů 27, 783 71 Olomouc, Czech Republic.

出版信息

Bioorg Med Chem Lett. 2020 Jul 1;30(13):127206. doi: 10.1016/j.bmcl.2020.127206. Epub 2020 Apr 21.

DOI:10.1016/j.bmcl.2020.127206
PMID:32354569
Abstract

Four gallium(III) complexes, [Ga(ClQ)]⋅MeOH (1 - MeOH), [Ga(ClQ)] (1), [Ga(BrQ)] (2), [Ga(dIQ)] (3) and [Ga(CQ)] (4), were prepared (H-ClQ = 5-chloro-8-quinolinol, H-BrQ = 7-bromo-8-quinolinol, H-dIQ = 5,7-diiodo-8-quinolinol, H-CQ = 5-chloro-7-iodo-8-quinolinol) and characterised by elemental analysis, IR and NMR spectroscopy. Single crystal structure analysis of 1 - MeOH confirmed that the complex has a molecular structure with gallium(III) metal ion coordinated in mer-fashion by N- and O-donor atoms of three ClQ ligands. Stability of all complexes in DMSO was proved by H NMR spectroscopy. The in vitro antiproliferative activity of 1 was evaluated against the A2780, MBA-MB-231 and HCT116 cell lines. Complex 1 displays higher antiproliferative activity (IC values in the range 2.1-6 μm) compared to the ClQ ligand and cisplatin; and a significant selective antiproliferative potency (IC = 136 μm, for normal MRC5pd30 cell line). Radical scavenging experiments revealed that complex 1 exhibits the highest antioxidant activity of the prepared complexes as well as the ligands.

摘要

四种镓(III)配合物,[Ga(ClQ)]⋅MeOH(1-MeOH)、[Ga(ClQ)](1)、[Ga(BrQ)](2)、[Ga(dIQ)](3)和[Ga(CQ)](4),被制备出来并通过元素分析、红外和核磁共振光谱进行了表征。1-MeOH 的单晶结构分析证实,该配合物具有分子结构,镓(III)金属离子以 mer 方式与三个 ClQ 配体的 N 和 O 供体原子配位。通过核磁共振光谱证明了所有配合物在 DMSO 中的稳定性。评估了 1 对 A2780、MBA-MB-231 和 HCT116 细胞系的体外增殖抑制活性。与 ClQ 配体和顺铂相比,配合物 1 显示出更高的增殖抑制活性(IC 值在 2.1-6 μm 范围内);并且对正常 MRC5pd30 细胞系具有显著的选择性增殖抑制作用(IC = 136 μm)。自由基清除实验表明,配合物 1 表现出最高的抗氧化活性,优于所制备的配合物和配体。

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