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Unravelling the mechanism of apoptosis induced by copper(II) complexes of NN2-pincer ligands in lung cancer cells
Dalton Transactions ( IF 3.5 ) Pub Date : 2024-07-24 , DOI: 10.1039/d4dt01075b Athulya Das 1 , Muniyandi Sankaralingam 1
Dalton Transactions ( IF 3.5 ) Pub Date : 2024-07-24 , DOI: 10.1039/d4dt01075b Athulya Das 1 , Muniyandi Sankaralingam 1
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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-N-(quinolin-8-yl)acetamide, L2(H) = 2-di-n-propylamino-N-(quinolin-8-yl)acetamide, L3(H) = 2-di-n-butylamino-N-(quinolin-8-yl)acetamide and L4(H) = 2-di-n-benzylamino-N-(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 IC50 value of 8 μM, showing no toxicity towards common L929 fibroblast cell lines (IC50 > 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 IC50 concentration. Furthermore, carboxy-H2DCFDA 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 in silico 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.
中文翻译：
揭示NN2-pincer配体铜(II)复合物诱导肺癌细胞凋亡的机制
高效化疗药物的发明对于人类健康和发展至关重要。记住这一点，一系列铜（ II ）钳配合物， 1-4 ，配体L1 （H）= 2-吗啉代-N- （喹啉-8-基）乙酰胺， L2 （H）= 2-二-正丙氨基-N- (喹啉-8-基)乙酰胺， L3 (H)=2-二-正丁氨基-N- (喹啉-8-基)乙酰胺和L4 (H)=2-二-n-苯甲基氨基-N- (喹啉-8-基)乙酰胺已被合成、表征并用于抑制癌症增殖。复合物1-4对肺癌 (A549) 和乳腺癌 (MCF-7) 癌细胞表现出非常有效的活性，根据世界卫生组织的数据，这两种癌症是最常诊断的癌症。其中1对肺癌细胞具有高度活性，IC 50值为8 μM，对常见的L929成纤维细胞系（IC 50 > 1000 μM）无毒性。此外，AO-EB染色推断这种细胞死亡归因于细胞凋亡，在IC 50浓度下通过流式细胞术测定为25.91%的细胞。此外，羧基-H 2 DCFDA染色揭示了ROS参与该机制。有趣的是，JC-1染料染色显示线粒体膜电位的变化，这表明线粒体中ROS的产生增强。 通过计算机研究对该机制的深入研究引导我们认识到复合物1-4可能会干扰线粒体中复合物 I 的功能。此外，这些研究可以扩展到临床应用，主要是吗啉附加复合物1 。
更新日期：2024-07-24
中文翻译：
揭示NN2-pincer配体铜(II)复合物诱导肺癌细胞凋亡的机制
高效化疗药物的发明对于人类健康和发展至关重要。记住这一点，一系列铜（ II ）钳配合物， 1-4 ，配体L1 （H）= 2-吗啉代-N- （喹啉-8-基）乙酰胺， L2 （H）= 2-二-正丙氨基-N- (喹啉-8-基)乙酰胺， L3 (H)=2-二-正丁氨基-N- (喹啉-8-基)乙酰胺和L4 (H)=2-二-n-苯甲基氨基-N- (喹啉-8-基)乙酰胺已被合成、表征并用于抑制癌症增殖。复合物1-4对肺癌 (A549) 和乳腺癌 (MCF-7) 癌细胞表现出非常有效的活性，根据世界卫生组织的数据，这两种癌症是最常诊断的癌症。其中1对肺癌细胞具有高度活性，IC 50值为8 μM，对常见的L929成纤维细胞系（IC 50 > 1000 μM）无毒性。此外，AO-EB染色推断这种细胞死亡归因于细胞凋亡，在IC 50浓度下通过流式细胞术测定为25.91%的细胞。此外，羧基-H 2 DCFDA染色揭示了ROS参与该机制。有趣的是，JC-1染料染色显示线粒体膜电位的变化，这表明线粒体中ROS的产生增强。 通过计算机研究对该机制的深入研究引导我们认识到复合物1-4可能会干扰线粒体中复合物 I 的功能。此外，这些研究可以扩展到临床应用，主要是吗啉附加复合物1 。
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