A highly cytotoxic Pd(II) saccharinate complex with tris(2-pyridylmethyl)amine acting through mitochondrial and ROS-induced DNA damage

İÇSEL YILMAZ C., Aydinlik S., AYGÜN M., YILMAZ V. T.

Inorganica Chimica Acta, vol.580, 2025 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 580
  • Publication Date: 2025
  • Doi Number: 10.1016/j.ica.2025.122590
  • Journal Name: Inorganica Chimica Acta
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, Compendex
  • Keywords: Anticancer activity, Apoptosis, Pd(II) complex, Saccharinate, Tris(2-pyridylmethyl)amine
  • Karadeniz Technical University Affiliated: Yes

Abstract

A novel Pd(II) complex containing saccharinate (sac) and tris(2-pyridylmethyl)amine (tpma) [Pd (sac)(tpma)](sac)⋅1.5H2O was synthesized and characterized by IR, ESI-MS, NMR spectroscopic methods, DTA/TG thermal analysis methods and single-crystal X-ray diffraction. The cationic Pd(II) complex displayed a distorted square planar coordination geometry with a N atom of sac and three N atoms of tpma, while another sac remained outside the coordination sphere as a counter ion. The sulforhodamine B (SRB) cell viability assay showed that the Pd(II) complex was found to be highly cytotoxic against four human cancer cell lines A549 (lung), HT29 (colon), MCF7 (breast), and LNCaP (prostate) in comparison with cisplatin. The complex demonstrated a remarkable selectivity toward MCF7 cells. Mechanistic studies indicated that the complex induced apoptosis in MCF7 cells based on annexin V/PI and caspase 3/7 assays. In addition, significant mitochondrial depolarization and increased intracellular ROS (reactive oxygen species) generation were observed in MCF7 cells exposed to the Pd(II) complex. The complex also caused ROS-induced DNA double strand breaks as evidenced by the γ-H2AX assay.