Unravelling the mechanism of apoptosis induced by copper(II) complexes of NN-pincer ligands in lung cancer cells.

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.