Lung cancer remains one of the leading causes of death worldwide. Due to the side effects of chemotherapeutic agents on normal cells and the development of resistance by cancer cells, there is an urgent need for alternative new pharmacological agents. Palladium (Pd)-conjugated Schiff base (SB) compounds represent an alternative approach with promising potential applications in cancer treatment. This study aims to identify novel therapeutic agents on A549 cells through the synthesis and characterization of Schiff base conjugated-Palladium complexes (Pd-L1 and Pd-L2). Additionally, it seeks to elucidate the mechanism of action of these compounds on both the A549 and NIH/3T3 cell lines. In the present study, two new Pd-L1 and Pd-L2 were synthesized for the first time and characterized mainly by single crystal X-ray diffraction and H, C, P NMR techniques. The cytotoxic effect of the compounds was evaluated by MTT assay on A549 and NIH/3T3 cell lines for 24 and 48 h. Cisplatin was used as a positive control group. Based on the cytotoxicity results, the complexes were evaluated for their anticancer activities against A549 cell lines for 48 h through reactive oxygen species (ROS), cell cycle, apoptotic, and necrotic cell analyses. The most potent cytotoxic effects were determined for Pd-L1 (IC: 23.33 μM), Pd-L2 (IC: 3.19 μM), and cisplatin (IC: 33.27 μM) on A549 cells (p < 0.05). The compounds exhibited a significant cytotoxic effect at lower concentrations on A549 cells compared to NIH/3T3 cells (p < 0.05). All compounds showed a significant increase in ROS levels in A549 cells compared to the control group (p < 0.05). While necrosis and apoptosis was observed in A549 cells treated with cisplatin, induction of apoptosis was effective in cell death for A549 cells treated with Pd-L1 and Pd-L2 (p < 0.05). Additionally, it was observed that the compounds inhibited cell proliferation in the G0/G1 and G2/M cell cycle phases (p < 0.05). All compounds induced cell cycle arrest and cell death in A549 cells by increasing ROS levels. The results obtained in the present study could advance the utilization of the compounds as anticancer agents.

中文翻译：

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新合成钯希夫碱金属配合物对非小细胞肺癌细胞系和小鼠胚胎成纤维细胞系的抗癌作用研究


肺癌仍然是全世界死亡的主要原因之一。由于化疗药物对正常细胞的副作用以及癌细胞产生耐药性，迫切需要替代的新药物。钯 (Pd) 共轭希夫碱 (SB) 化合物代表了一种替代方法，在癌症治疗中具有广阔的潜在应用前景。本研究旨在通过希夫碱缀合钯复合物（Pd-L1 和 Pd-L2）的合成和表征来鉴定针对 A549 细胞的新型治疗剂。此外，它还试图阐明这些化合物对 A549 和 NIH/3T3 细胞系的作用机制。本研究首次合成了两种新型Pd-L1和Pd-L2，并主要通过单晶X射线衍射和H、C、P NMR技术对其进行了表征。通过MTT测定对A549和NIH/3T3细胞系24和48小时评估化合物的细胞毒作用。顺铂用作阳性对照组。根据细胞毒性结果，通过活性氧（ROS）、细胞周期、凋亡和坏死细胞分析评估复合物对A549细胞系48小时的抗癌活性。 Pd-L1 (IC50: 23.33 μM)、Pd-L2 (IC50: 3.19 μM) 和顺铂 (IC50: 33.27 μM) 对 A549 细胞具有最强的细胞毒性作用 (p < 0.05)。与 NIH/3T3 细胞相比，这些化合物在较低浓度下对 A549 细胞表现出显着的细胞毒性作用 (p < 0.05)。与对照组相比，所有化合物均显示 A549 细胞中 ROS 水平显着增加 (p < 0.05)。 虽然在用顺铂处理的 A549 细胞中观察到坏死和细胞凋亡，但诱导细胞凋亡对于用 Pd-L1 和 Pd-L2 处理的 A549 细胞的细胞死亡是有效的 (p < 0.05)。此外，还观察到这些化合物抑制 G0/G1 和 G2/M 细胞周期期的细胞增殖 (p < 0.05)。所有化合物均通过增加 ROS 水平诱导 A549 细胞的细胞周期停滞和细胞死亡。本研究中获得的结果可以促进这些化合物作为抗癌药物的利用。