Bioinspired & Biomimetic Inorganic Chemistry Laboratory, Department of Chemistry, National Institute of Technology Calicut, Kozhikode-673601, Kerala, India.
Dalton Trans. 2024 Aug 27;53(34):14364-14377. doi: 10.1039/d4dt01075b.
The invention of efficient chemotherapeutic drugs is essential for human health and development. Keeping this in mind, a series of copper(II) pincer complexes, 1-4, of ligands L1(H) = 2-morpholino--(quinolin-8-yl)acetamide, L2(H) = 2-di--propylamino--(quinolin-8-yl)acetamide, L3(H) = 2-di--butylamino--(quinolin-8-yl)acetamide and L4(H) = 2-di--benzylamino--(quinolin-8-yl)acetamide have been synthesized, characterized, and utilized for inhibiting cancer proliferation. Complexes 1-4 showed very efficient activity against lung (A549) and breast (MCF-7) cancer cells, which are the most frequently diagnosed cancers according to the WHO. Among them, 1 was highly active against lung cancer cells with an IC value of 8 μM, showing no toxicity towards common L929 fibroblast cell lines (IC > 1000 μM). Moreover, AO-EB staining inferred that this cellular demise was attributed to apoptosis, which was determined to be 25.91% of cells by flow cytometry at the IC concentration. Furthermore, carboxy-HDCFDA staining revealed the involvement of ROS in the mechanism. Interestingly, JC-1 dye staining revealed a change in the potential of the mitochondrial membrane, which indicates the enhanced production of ROS in mitochondria. A deep search for the mechanism through studies guided us to the fact that complexes 1-4 might perturb the function of complex I in mitochondria. Furthermore, the studies can be expanded towards clinical applications mainly with morpholine appended complex 1.
发明高效的化疗药物对于人类的健康和发展至关重要。基于这一考虑，我们合成了一系列铜（II）钳形配合物 1-4，其配体 L1(H) = 2-吗啉基-（8-喹啉基）乙酰胺、L2(H) = 2-二异丙基氨基-（8-喹啉基）乙酰胺、L3(H) = 2-二丁基氨基-（8-喹啉基）乙酰胺和 L4(H) = 2-二苄基氨基-（8-喹啉基）乙酰胺。这些配合物已被合成、表征，并用于抑制癌症增殖。配合物 1-4 对肺癌（A549）和乳腺癌（MCF-7）细胞表现出非常高效的活性，这两种癌症是根据世界卫生组织的诊断最为常见的癌症。其中，1 对肺癌细胞具有很高的活性，IC 值为 8 μM，对常见的 L929 成纤维细胞系没有毒性（IC > 1000 μM）。此外，AO-EB 染色推断这种细胞死亡归因于细胞凋亡，通过流式细胞术在 IC 浓度下确定凋亡率为 25.91%。此外，羧基-HDCFDA 染色显示 ROS 参与了这一机制。有趣的是，JC-1 染色显示线粒体膜电位发生变化，这表明线粒体中 ROS 的产生增强。通过研究深入探讨其机制，我们发现配合物 1-4 可能会干扰线粒体中复合物 I 的功能。此外，这些研究可以通过扩展到临床应用主要针对含吗啉基的配合物 1 来进行。
