Synthesis, properties, antitumor and antibacterial activity of new Pt(II) and Pd(II) complexes with 2,2'-dithiobis(benzothiazole) ligand

Bioorg Med Chem. 2017 Apr 15;25(8):2378-2386. doi: 10.1016/j.bmc.2017.02.067. Epub 2017 Mar 9.

Abstract

Mono- and binuclear Pt(II) and Pd(II) complexes with 2,2'-dithiobis(benzothiazole) (DTBTA) ligand are reported. [Pt(DTBTA)(DMSO)Cl]Cl∙CHCl3 (1) and [Pd2(µ-Cl)2(DTBTA)2]Cl2 (2) have been synthesized and structurally characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy, MS spectrometry and the content of platinum and palladium was determined using a flame atomic spectrometer. Two different coordination modes of 1 and 2 complexes were found; in both complexes, the coordination of Pt(II) and Pd(II) ions involves the N(3) atoms of the ligand but the binuclear complex 2, is a cis-chloro-bridged palladium complex. Evaluation of their in vitro antitumor activity against two human tumor cell lines human breast cancer (MCF-7) and hepatocellular carcinoma (HepG2); and their antimicrobial activity against Escherichia coli and Kokuria rhizophila was performed. Only complex 1 showed a dose- and time-dependent cytotoxic activity against the two tumor cell lines, associated to apoptosis and accumulation of treated cells in G0/G1 phase of cell cycle, while both 1 and 2 exhibited antimicrobial activity with complex 1 much more potent. The study on intracellular uptake in both MCF-7 and HepG2 cell lines revealed that only platinum of complex 1 is present inside the cells, suggesting a different mode of action of the two compounds. This was also in agreement with the results obtained for the antitumor and antibacterial activity.

Keywords: Anticancer activity; Antimicrobial activity; Heterocyclic nitrogen ligand; Palladium complex; Platinum complex.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Benzothiazoles / pharmacology*
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Escherichia coli / drug effects
  • Humans
  • Ligands
  • Microbial Sensitivity Tests
  • Palladium / chemistry*
  • Palladium / pharmacology*
  • Platinum Compounds / chemical synthesis
  • Platinum Compounds / chemistry*
  • Platinum Compounds / pharmacology*
  • Spectrum Analysis

Substances

  • Anti-Bacterial Agents
  • Benzothiazoles
  • Ligands
  • Platinum Compounds
  • Palladium