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
{"title":"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。","authors":"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","doi":"10.1002/ddr.22265","DOIUrl":null,"url":null,"abstract":"<p>Four lanthanide complexes with 8-hydroxyquinoline-2-aldehyde-2-hydrazinopyridine (H-L<sup>1</sup>), 8-hydroxyquinoline-2-aldehyde-2-hydrazimidazole (H-L<sup>2</sup>): [Sm(L<sup>1</sup>)<sub>2</sub>][Sm(L<sup>1</sup>)(NO<sub>3</sub>)<sub>3</sub>]<b>·</b>CHCl<sub>3</sub><b>·</b>2CH<sub>3</sub>OH (<b>1</b>), [Gd(L<sup>1</sup>)<sub>2</sub>][Gd(L<sup>1</sup>)(NO<sub>3</sub>)<sub>3</sub>]<b>·</b>CHCl<sub>3</sub><b>·</b>2CH<sub>3</sub>OH (<b>2</b>), [Sm(L<sup>2</sup>)(NO<sub>3</sub>)<sub>2</sub>]<sub>2</sub><b>·</b>CH<sub>3</sub>OH (<b>3</b>), and [Eu(L<sup>2</sup>)(NO<sub>3</sub>)<sub>2</sub>]<sub>2</sub><b>·</b>CH<sub>3</sub>OH (<b>4</b>) 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 <b>1</b> showed the best antiproliferative activity against NCI-H460 tumor cells. Mechanistic studies demonstrated that complex <b>1</b> 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 Ca<sup>2+</sup> levels and reactive oxygen species generation. In addition, complex <b>1</b> affected the expression levels of intracellular apoptosis-related proteins and activated the caspase-3/9 in NCI-H460 cells. Therefore, complex <b>1</b> is a potential anticancer agent.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"85 7","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"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\",\"doi\":\"10.1002/ddr.22265\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Four lanthanide complexes with 8-hydroxyquinoline-2-aldehyde-2-hydrazinopyridine (H-L<sup>1</sup>), 8-hydroxyquinoline-2-aldehyde-2-hydrazimidazole (H-L<sup>2</sup>): [Sm(L<sup>1</sup>)<sub>2</sub>][Sm(L<sup>1</sup>)(NO<sub>3</sub>)<sub>3</sub>]<b>·</b>CHCl<sub>3</sub><b>·</b>2CH<sub>3</sub>OH (<b>1</b>), [Gd(L<sup>1</sup>)<sub>2</sub>][Gd(L<sup>1</sup>)(NO<sub>3</sub>)<sub>3</sub>]<b>·</b>CHCl<sub>3</sub><b>·</b>2CH<sub>3</sub>OH (<b>2</b>), [Sm(L<sup>2</sup>)(NO<sub>3</sub>)<sub>2</sub>]<sub>2</sub><b>·</b>CH<sub>3</sub>OH (<b>3</b>), and [Eu(L<sup>2</sup>)(NO<sub>3</sub>)<sub>2</sub>]<sub>2</sub><b>·</b>CH<sub>3</sub>OH (<b>4</b>) 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 <b>1</b> showed the best antiproliferative activity against NCI-H460 tumor cells. Mechanistic studies demonstrated that complex <b>1</b> 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 Ca<sup>2+</sup> levels and reactive oxygen species generation. In addition, complex <b>1</b> affected the expression levels of intracellular apoptosis-related proteins and activated the caspase-3/9 in NCI-H460 cells. Therefore, complex <b>1</b> is a potential anticancer agent.</p>\",\"PeriodicalId\":11291,\"journal\":{\"name\":\"Drug Development Research\",\"volume\":\"85 7\",\"pages\":\"\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-10-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Development Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ddr.22265\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Development Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ddr.22265","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
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
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.
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.
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