Trans-Pd/Pt(II) saccharinate complexes with a phosphine ligand: Synthesis, cytotoxicity and structure-activity relationship


Icsel C., YILMAZ V. T. , AYGÜN M., Ulukaya E.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol.30, no.9, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 30 Issue: 9
  • Publication Date: 2020
  • Doi Number: 10.1016/j.bmcl.2020.127077
  • Journal Name: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: Trans-Pd/Pt complexes, Saccharinate, Phosphine, DNA damage, Cytotoxicity, ASCITES-CARCINOMA EAC, ANTIPROLIFERATIVE ACTIVITY, PLATINUM(II) COMPLEXES, ANTICANCER ACTIVITY, STRAND BREAKS, IN-VITRO, PALLADIUM(II), DNA, CELLS, TERPYRIDINE
  • Karadeniz Technical University Affiliated: No

Abstract

New trans-[Pd(sac)(2)(PPhMe2)(DMSO)]center dot H2O (Pd) and trans-[Pt(sac)(2)(PPhMe2)(2)]center dot H2O (Pt) complexes (sac = saccharinate and PPhMe 2 = dimethylphenylphosphine) were synthesized and characterized by elemental analysis, IR, NMR, ESI-MS spectral analyses and X-ray diffraction. The complexes were evaluated for their in vitro cytotoxicity against breast (MCF-7), colon (HCT116) and lung (A549) human cancer cell lines. The ATP viability assay displayed that Pd was biologically inactive, but Pt showed significant anticancer potency on MCF-7 cancer cells, similar to cisplatin. The results suggested that Pt targeted DNA, whereas Pd displayed higher binding affinity towards human serum albumin (HSA). Mechanism of action studies of Pt suggested apoptotic cell death due to significant increase in intracellular ROS (reactive oxygen species) levels, mitochondrial damage and formation of DNA double-strand breaks. Finally, this work represents a new example of potent transplatin anticancer complexes.