Sm(Ⅲ), Gd(Ⅲ), and Eu(Ⅲ) complexes with 8-hydroxyquinoline derivatives as potential anticancer agents via inhibiting cell proliferation, blocking cell cycle, and inducing apoptosis in NCI-H460 cells

IF 3.5 4区医学 Q2 CHEMISTRY, MEDICINAL Drug Development Research Pub Date : 2024-10-02 DOI:10.1002/ddr.22265

Kun Yang, Huan-Qing Li, Mei-Qi Hu, Meng-Xue Ma, Yun-Qiong Gu, Qi-Yuan Yang, Muhammad Iqbal Choudhary, Hong Liang, Zhen-Feng Chen

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Abstract

Four lanthanide complexes with 8-hydroxyquinoline-2-aldehyde-2-hydrazinopyridine (H-L¹), 8-hydroxyquinoline-2-aldehyde-2-hydrazimidazole (H-L²): [Sm(L¹)₂][Sm(L¹)(NO₃)₃]·CHCl₃·2CH₃OH (1), [Gd(L¹)₂][Gd(L¹)(NO₃)₃]·CHCl₃·2CH₃OH (2), [Sm(L²)(NO₃)₂]₂·CH₃OH (3), and [Eu(L²)(NO₃)₂]₂·CH₃OH (4) were synthesized and characterized. In vitro cytotoxicity evaluation showed that the ligands and four lanthanide complexes exhibited cytotoxicity to the five tested tumor cell lines. Among them, complex 1 showed the best antiproliferative activity against NCI-H460 tumor cells. Mechanistic studies demonstrated that complex 1 arrested the cell cycle of NCI-H460 cells in G1 phase and induced mitochondria-mediated apoptosis, which resulted in the loss of mitochondrial membrane potential, enhanced intracellular Ca²⁺ levels and reactive oxygen species generation. In addition, complex 1 affected the expression levels of intracellular apoptosis-related proteins and activated the caspase-3/9 in NCI-H460 cells. Therefore, complex 1 is a potential anticancer agent.

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8-羟基喹啉衍生物与 Sm(Ⅲ)、Gd(Ⅲ)和 Eu(Ⅲ)配合物通过抑制 NCI-H460 细胞增殖、阻滞细胞周期和诱导细胞凋亡而成为潜在的抗癌剂。

四种镧系元素与 8-羟基喹啉-2-甲醛-2-肼基吡啶（H-L1）、8-羟基喹啉-2-甲醛-2-肼基咪唑（H-L2）的配合物：合成并表征了[Sm(L1)2][Sm(L1)(NO3)3]-CHCl3-2CH3OH（1）、[Gd(L1)2][Gd(L1)(NO3)3]-CHCl3-2CH3OH（2）、[Sm(L2)(NO3)2]2-CH3OH（3）和[Eu(L2)(NO3)2]2-CH3OH（4）。体外细胞毒性评估显示，配体和四种镧系配合物对五种受测肿瘤细胞株具有细胞毒性。其中，复合物 1 对 NCI-H460 肿瘤细胞的抗增殖活性最佳。机理研究表明，复合物 1 可使 NCI-H460 细胞的细胞周期停滞在 G1 期，并诱导线粒体介导的细胞凋亡，导致线粒体膜电位丧失、细胞内 Ca2+ 水平升高和活性氧生成。此外，复合物 1 还影响细胞内凋亡相关蛋白的表达水平，并激活 NCI-H460 细胞中的 caspase-3/9。因此，复合物 1 是一种潜在的抗癌剂。

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来源期刊

Drug Development Research 医学-药学

CiteScore

6.40

自引率

2.60%

发文量

104

审稿时长

6-12 weeks

期刊介绍： Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.