Jakovljevic Stefan, Canovic Petar, Spasic Marko, Zivkovic Marija, Zaric Milan, Zivkovic Zaric Radica, Franich Andjela, Rajkovic Snezana, Todorovic Zeljko, Relic Nenad, Zivic Milos, Mirkovic Nikola
Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Svetozar Markovic Street 69, 34000 Kragujevac, Serbia.
Department of General Surgery, University Clinical Center Kragujevac, Zmaj Jovina Street 30, 34000 Kragujevac, Serbia.
Molecules. 2025 Mar 30;30(7):1534. doi: 10.3390/molecules30071534.
This study investigates the synthesis, characterization, and cytotoxicity of dinuclear palladium(II) complexes with glycine (Pd1), alanine (Pd2), and methionine (Pd3) as ligands. UV-Vis and fluorescence spectroscopy were used to investigate the complexes' interactions with calf thymus DNA (CT-DNA) and bovine serum albumin. The obtained measurements demonstrate that Pd1 and Pd2 have stronger binding affinities for CT-DNA compared to Pd3, with Pd3 exhibiting the most significant cytotoxicity against the MDA-MB-231 cancer cell line. The binding behavior was quantified by calculating intrinsic binding constants (K) and Stern-Volmer constants (K), showing that Pd1 and Pd2 interact more effectively with DNA, possibly due to less steric hindrance in their chelation. Cytotoxic activity was evaluated using an MTT assay, and the results confirm that Pd3, with methionine as the ligand, exhibited superior antitumor effects, inducing apoptosis through caspase-3 activation. The complexes also showed a strong affinity for BSA, indicating their potential for biological interaction. These discoveries shed light on the processes of palladium(II) complexes in biological systems, highlighting their DNA and protein-binding capabilities, as well as their anticancer potential. Further research is required to explore their pharmacokinetics and possible clinical applications.
本研究考察了以甘氨酸（Pd1）、丙氨酸（Pd2）和蛋氨酸（Pd3）为配体的双核钯（II）配合物的合成、表征及细胞毒性。采用紫外-可见光谱和荧光光谱研究了这些配合物与小牛胸腺DNA（CT-DNA）和牛血清白蛋白的相互作用。所得测量结果表明，与Pd3相比，Pd1和Pd2对CT-DNA具有更强的结合亲和力，其中Pd3对MDA-MB-231癌细胞系表现出最显著的细胞毒性。通过计算固有结合常数（K）和斯特恩-沃尔默常数（K）对结合行为进行了量化，结果表明Pd1和Pd2与DNA的相互作用更有效，这可能是由于它们螯合时的空间位阻较小。使用MTT法评估细胞毒性活性，结果证实以蛋氨酸为配体的Pd3表现出优异的抗肿瘤作用，通过激活caspase-3诱导细胞凋亡。这些配合物还对牛血清白蛋白表现出很强的亲和力，表明它们具有生物相互作用的潜力。这些发现揭示了钯（II）配合物在生物系统中的作用过程，突出了它们与DNA和蛋白质的结合能力以及它们的抗癌潜力。需要进一步研究以探索它们的药代动力学和可能的临床应用。
