In vitro study of the pro-apoptotic mechanism of amino acid Schiff base copper complexes on anaplastic thyroid cancer

作者：Peiran Zhao, Xinyan Zhang, Jianfang Dong, Lianzhi Li, Xiao Chen Meng, Lei Gao · 发表于：European Journal of Pharmaceutical Sciences · 年份：2025 · DOI：10.1016/j.ejps.2025.107005 · 被引用次数：17 · 研究领域：Metal complexes synthesis and properties、Ferrocene Chemistry and Applications、Synthesis and Characterization of Heterocyclic Compounds

• Three five-coordinated polyhedron amino acid Schiff base copper (II) complexes were designed and characterized as potential anti-tumor drugs in this research. • Complex 1 exhibits excellent cytotoxicity with IC 50 values of 0.59±0.05 μM, 2.36±0.47 μM, 1.24±0.11 μM, 0.75±0.09 μM, 1.72±0.06 μM towards five thyroid cancer cell lines. • Complex 1 can effectively inhibit cancer cell growth mainly through mitochondrial dysfunction, intracellular ROS accumulation, and ROS-mediated DNA damage. • Complex 1 may induce apoptosis in ARO cells via ROS-mediated downregulation of Akt and p38 MAPK activation and displays excellent antitumor activity. In the endocrine system, anaplastic thyroid cancer (ATC) is extremely aggressive since it inhibits the majority of medications and treatments. Therefore, there is an immediate demand to identify new treatment approaches or drugs to deal with ATC. Recently, amino acid Schiff base copper complexes have received great attention due to their excellent anti-tumor activity. In this research, three copper(II) complexes, [Cu( o -van-D-Trp)(phen)] (1) , [Cu( o -van-D-Trp)(bipy)] (2) , [Cu(naph-D-Trp)(bipy)] (3) , [D-Trp = D-tryptophan; o-van = o -vanillin; naph = 2‑hydroxy-1- naphthaldehyde; phen = 1,10-phenanthroline; bipy = 2,2-biprydine], have been synthesized and investigated as potential anticancer agents. The crystal structure data of the complexes demonstrate that the central copper (II) atom forms a twisted polyhedral environment with nitrogen ...