State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, Guilin 541004, PR China.
International Center for Chemical and Biological Sciences, University of Karachi, Karachi 74270, Pakistan.
J Inorg Biochem. 2020 Dec;213:111260. doi: 10.1016/j.jinorgbio.2020.111260. Epub 2020 Sep 28.
Two copper complexes, Cu1 (CuLCl, L = 2-(6,7-dimethoxyisoquinolin-1-yl) aniline) and Cu2 (CuLCl, L = 2-(6-methoxyisoquinolin-1-yl) aniline), were synthesized and characterized. These complexes exhibited high cytotoxic activity toward different cancer cell lines, including the A549 lung cancer cell line, and low cytotoxicity toward normal human cells. Mechanistic studies have shown that these complexes induce bimodal death of cancer cells through apoptosis and autophagy, including the activation of apoptotic and autophagic cell signaling pathways. In addition, Cu1 and Cu2 interacted with calf thymus DNA (ct-DNA) via an intercalative binding mode. The different biological behaviors of these copper complexes could be attributed to the presence of electron-donating methoxy groups on the ligands. Cu1 and Cu2 effectively inhibited tumor growth in a xenografted mouse model bearing A549 cells but exhibited lower in vivo toxicity than cisplatin. Thus, Cu1 and Cu2 can be developed as potential anticancer agents.
两种铜配合物，Cu1（CuLCl，L=2-（6,7-二甲氧基异喹啉-1-基）苯胺）和 Cu2（CuLCl，L=2-（6-甲氧基异喹啉-1-基）苯胺），被合成并进行了表征。这些配合物对不同的癌细胞系具有高细胞毒性，包括 A549 肺癌细胞系，对正常人类细胞的细胞毒性较低。机制研究表明，这些配合物通过细胞凋亡和自噬诱导癌细胞的双模态死亡，包括凋亡和自噬细胞信号通路的激活。此外，Cu1 和 Cu2 通过嵌入结合模式与小牛胸腺 DNA（ct-DNA）相互作用。这些铜配合物的不同生物学行为可以归因于配体上存在供电子的甲氧基。Cu1 和 Cu2 有效地抑制了携带 A549 细胞的异种移植小鼠模型中的肿瘤生长，但体内毒性低于顺铂。因此，Cu1 和 Cu2 可以开发为潜在的抗癌药物。
