Scholarlink

<p>The development of selective anticancer agents remains a central objective in medicinal chemistry. Here, we report the synthesis, structural characterization, and biological evaluation of the first metal complex of a quinoline-based thiazolyl-hydrazone ligand [(<i>E</i>)-2-(8-(quinolin-2-ylmethylene)hydrazinyl)-4-(4-tolyl)-1,3-thiazole)] (<b>HL</b>). Obtained octahedral Zn(II) complex [Zn(HL)<sub>2</sub>](NO<sub>3</sub>)<sub>2</sub>, (<b>1</b>), is based on two <i>NNN</i> tridentate coordinated ligands. In vitro cytotoxicity assays revealed that the complex exhibits potent and selective activity against lung adenocarcinoma A-549 and colorectal carcinoma HCT-116, while sparing non-tumorigenic human embryonic kidney HEK-293 cells. Mechanistic studies demonstrated that the complex induces S-phase arrest, inhibits DNA synthesis, and triggers significant DNA damage as indicated by increased p-γH2AX expression. These effects were accompanied by mitochondrial depolarization, caspase-3/7 activation, and phosphatidylserine externalization, confirming apoptosis via the intrinsic pathway. The compound further inhibited tumor growth in 3D spheroids and the chick chorioallantoic membrane model without overt toxicity. Compared to the free ligand and reference chemotherapeutics, the zinc complex showed improved efficacy and selectivity. These results highlight the potential of metal coordination to enhance the biological activity of hybrid ligands, supporting further development of this class of compounds as selective anticancer agents.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Zinc complex with quinoline-based thiazolyl-hydrazone targeting DNA replication in cancer cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月22日

查看全文
  • Natalia Maciejewska,
  • Јоvana Araškov,
  • Mateusz Olszewski,
  • Aleksandar Višnjevac,
  • Nenad Filipović,
  • Magdalena Stevanović,
  • Berta Barta Holló,
  • Tamara Todorović,
  • Nenad Filipović

摘要

The development of selective anticancer agents remains a central objective in medicinal chemistry. Here, we report the synthesis, structural characterization, and biological evaluation of the first metal complex of a quinoline-based thiazolyl-hydrazone ligand [(E)-2-(8-(quinolin-2-ylmethylene)hydrazinyl)-4-(4-tolyl)-1,3-thiazole)] (HL). Obtained octahedral Zn(II) complex [Zn(HL)2](NO3)2, (1), is based on two NNN tridentate coordinated ligands. In vitro cytotoxicity assays revealed that the complex exhibits potent and selective activity against lung adenocarcinoma A-549 and colorectal carcinoma HCT-116, while sparing non-tumorigenic human embryonic kidney HEK-293 cells. Mechanistic studies demonstrated that the complex induces S-phase arrest, inhibits DNA synthesis, and triggers significant DNA damage as indicated by increased p-γH2AX expression. These effects were accompanied by mitochondrial depolarization, caspase-3/7 activation, and phosphatidylserine externalization, confirming apoptosis via the intrinsic pathway. The compound further inhibited tumor growth in 3D spheroids and the chick chorioallantoic membrane model without overt toxicity. Compared to the free ligand and reference chemotherapeutics, the zinc complex showed improved efficacy and selectivity. These results highlight the potential of metal coordination to enhance the biological activity of hybrid ligands, supporting further development of this class of compounds as selective anticancer agents.