Cytotoxic effects of Pd(II) complexes on cancer and normal cells: Their DNA & BSA adduct formation and theoretical approaches

Bioorg Chem. 2022 Nov:128:106093. doi: 10.1016/j.bioorg.2022.106093. Epub 2022 Aug 12.

Abstract

Herein, we report the synthesis and characterisation of a series of Pd(II) complexes: Pd(TEEDA)Cl2, C-1; [Pd(TEEDA)(OH2)2](NO3)2, C-2; [Pd(TEEDA)(l-cys)](NO3)2, C-3; [Pd(TEEDA)(NALC)], C-4; [Pd(TEEDA)(Meth)](NO3)2, C-5; and [Pd(TEEDA)(GSH)], C-6 (where TEEDA = N,N,N'-Triethylenediamine, l-cys = l-cysteine, NALC = N-acetyl-l-cysteine, Meth = dl-methionine and GSH = glutathione). UV-Vis spectroscopic characterisation was supported by TD-DFT theoretical simulation using Gaussian09 software. Different reactivity parameters were calculated from the energy difference between HOMO and LUMO of the complexes by DFT. The bonding mode of the labile ligands was confirmed by NBO analysis. Interaction of the complexes with DNA has been observed by gel electrophoresis experiment. DNA binding nature as well as binding constants of the complexes were measured with UV-Vis and fluorescence spectroscopic method. The binding nature of the complexes with DNA was confirmed by viscometric titration. Interaction of the complexes with BSA was investigated by UV-Vis and fluorescence titration method. Cytotoxic activity of the Pd(II) complexes was evaluated on A549 (lung carcinoma epithelial cells), HCT116(Colorectal Carcinoma) and HEK293 (Human embryonic kidney cells) cell lines. The ROS generation in the presence of the complexes was tested both on cancer cell lines A549 and HCT116 as well as human normal cell HEK293.

Keywords: DNA & BSA binding; Molecular docking; Pd(II) complex; ROS generation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • DNA / chemistry
  • HEK293 Cells
  • Humans
  • Molecular Docking Simulation
  • Neoplasms* / drug therapy
  • Palladium / chemistry
  • Palladium / pharmacology
  • Serum Albumin, Bovine / chemistry

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Serum Albumin, Bovine
  • Palladium
  • DNA