Hussain Shazia, Masood Sara, Hussain Shabeeb, Hussain Irfan, Malik Fouzia, Akhtar Muhammad Nadeem, Zafar M Naveed
Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan.
Department of Applied and Environmental Chemistry and Interdisciplinary Excellence Centre, Institute of Chemistry, University of Szeged, Rerrich B´ Ela T´ Er 1, Szeged, 6720, Hungary.
Biometals. 2025 Jun 5. doi: 10.1007/s10534-025-00702-9.
Pd(II)-containing complexes exhibit considerable potential as therapeutic agents against cancer owing to their proficiency in selectively targeting neoplastic cells compared to cisplatin. In this context, we describe the synthesis of square planar palladium complexes of the general formula [Pd(L)] from imino-amido-based asymmetrical (NN) proligands (HL) and characterized based on melting point, CHN analysis, spectroscopic techniques (FT-IR, H NMR, C NMR), and ESI-MS. DFT computations are employed to elucidate the characteristics of the frontier orbitals and MEP analysis. In the current investigation, the precursors, proligands, Pd(II) complexes and cisplatin were systematically assessed for their anticancer efficacy against breast carcinoma (BT-474, BT-483, and BT-459) by MTT assay. Among the compounds subjected to evaluation, the complex [Pd(L)] demonstrated superior capacity in inhibiting the proliferation of breast cancer cells, exhibiting median inhibitory concentration (IC) values of 6.10, 9.01, and 7.20 µM than standard cisplatin (IC = 18.70, 19.40, 19.30 µM), respectively. Cellular apoptosis assessment of [Pd(L)] exhibited characteristic apoptotic phenomena including membrane blebbing and DNA condensation. Furthermore, electronic spectroscopy was used to evaluate the binding modalities of complexes with CT DNA, supported by the in silico docking studies. [Pd(L)] exhibited the mixed binding mode with a binding affinity in the range of 10 M.
含钯（II）配合物作为抗癌治疗剂具有相当大的潜力，因为与顺铂相比，它们能够选择性地靶向肿瘤细胞。在此背景下，我们描述了由亚氨基酰胺基不对称（NN）前体配体（HL）合成通式为[Pd(L)]的平面正方形钯配合物，并通过熔点、CHN分析、光谱技术（傅里叶变换红外光谱、氢核磁共振、碳核磁共振）和电喷雾电离质谱对其进行了表征。采用密度泛函理论计算来阐明前沿轨道的特征和分子静电势分析。在当前的研究中，通过MTT法系统评估了前体、前体配体、钯（II）配合物和顺铂对乳腺癌（BT - 474、BT - 483和BT - 459）的抗癌疗效。在接受评估的化合物中，配合物[Pd(L)]在抑制乳腺癌细胞增殖方面表现出卓越的能力，其半数抑制浓度（IC）值分别为6.10、9.01和7.20 μM，优于标准顺铂（IC = 18.70、19.40、19.30 μM）。[Pd(L)]的细胞凋亡评估显示出包括细胞膜起泡和DNA凝聚在内的典型凋亡现象。此外，电子光谱用于评估配合物与CT DNA的结合模式，并得到了计算机模拟对接研究的支持。[Pd(L)]表现出混合结合模式，结合亲和力在10 M范围内。
