Pantic Damnjan, Mirkovic Nikola, Vulovic Tatjana, Jovanovic Danijela, Jakovljevic Stefan, Canovic Petar, Zaric Milan, Zaric Radica Zivkovic, Kostic Marina, Dragojevic Jovana, Divac Vera, Milanovic Ziko, Milisavljevic Kristina, Mitrovic Marina, Zelen Ivanka
Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Department of Urology, Clinic of Urology and Nephrology, University Clinical Center Kragujevac, Kragujevac, Serbia.
Front Chem. 2025 Jul 17;13:1636477. doi: 10.3389/fchem.2025.1636477. eCollection 2025.
Palladium (II) complexes are promising anticancer agents with potential advantages over platinum drugs. This study aimed to synthesize and characterize three new Pd(II) complexes () with Schiff base ligands derived from salicylic acid and amine scaffolds, and to evaluate their antitumor activity against prostate cancer cells.
The Pd(II) complexes were synthesized and structurally characterized. Cytotoxicity was tested on two human prostate cancer cell lines (PC-3, DU-145) and healthy fibroblasts (MRC-5). Apoptosis induction was assessed by flow cytometry, with a focus on Bcl-2 and caspase proteins. Molecular docking was used to examine binding to the androgen receptor (AR) and apoptotic regulators (CASP3, BCL2, BAX). DNA and human serum albumin (HSA) binding were also investigated.
All complexes showed significant cytotoxicity. Notably, complex exhibited more potent cytotoxic activity than cisplatin in prostate cancer cell lines, with lower IC values after 72 h exposure in DU-145 (7.1 µM vs. 8.2 µM) and PC-3 cells (8.6 µM vs. 21.9 µM), while showing reduced toxicity in normal MRC-5 cells (42.3 µM vs. 24.4 µM). Apoptosis was confirmed as the primary cytotoxic mechanism, involving the activation of Bcl-2 and caspases. Docking studies revealed that complex had the strongest binding affinity to AR and apoptotic proteins, mediated by hydrogen bonds, π-π stacking, and hydrophobic interactions. DNA and HSA binding supported their biological relevance.
Complex exhibits potent anticancer activity through the induction of apoptosis and dual targeting of the AR and apoptotic pathways, making it a promising candidate for further development of anticancer drugs.
钯（II）配合物是很有前景的抗癌药物，与铂类药物相比具有潜在优势。本研究旨在合成并表征三种新的钯（II）配合物（），其配体为源自水杨酸和胺骨架的席夫碱配体，并评估它们对前列腺癌细胞的抗肿瘤活性。
合成并对钯（II）配合物进行结构表征。在两种人前列腺癌细胞系（PC-3、DU-145）和健康成纤维细胞（MRC-5）上测试细胞毒性。通过流式细胞术评估凋亡诱导情况，重点关注Bcl-2和半胱天冬酶蛋白。使用分子对接来研究与雄激素受体（AR）和凋亡调节因子（CASP3、BCL2、BAX）的结合。还研究了与DNA和人血清白蛋白（HSA）的结合。
所有配合物均表现出显著的细胞毒性。值得注意的是，配合物在前列腺癌细胞系中表现出比顺铂更强的细胞毒性活性，在DU-145细胞（72小时暴露后IC值为7.1 μM对8.2 μM）和PC-3细胞（8.6 μM对21.9 μM）中更低，同时在正常MRC-5细胞中显示出较低的毒性（42.3 μM对24.4 μM）。凋亡被确认为主要的细胞毒性机制，涉及Bcl-2和半胱天冬酶的激活。对接研究表明，配合物与AR和凋亡蛋白具有最强的结合亲和力，通过氢键、π-π堆积和疏水相互作用介导。与DNA和HSA的结合支持了它们的生物学相关性。
配合物通过诱导凋亡以及对AR和凋亡途径的双重靶向表现出强大的抗癌活性，使其成为抗癌药物进一步开发的有前景的候选物。
