Structures and anticancer activity of chlorido platinum(II) saccharinate complexes with mono- and dialkylphenylphosphines

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

JOURNAL OF INORGANIC BIOCHEMISTRY, cilt.195, ss.39-50, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 195
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.jinorgbio.2019.03.008
  • Dergi Adı: JOURNAL OF INORGANIC BIOCHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.39-50
  • Anahtar Kelimeler: Pt(II) complex, Saccharinate, Phosphine, DNA binding, Cytotoxicity, Anticancer mechanism, ASCITES-CARCINOMA EAC, ANTIPROLIFERATIVE ACTIVITY, PHOSPHORUS LIGANDS, ANTITUMOR-ACTIVITY, PHOSPHINE-LIGANDS, IN-VITRO, PALLADIUM(II), DNA, CISPLATIN, TERPYRIDINE
  • Karadeniz Teknik Üniversitesi Adresli: Hayır

Özet

cis-[PtCl(sac)(PPh2Me)(2)] (1), cis-[PtCl(sac)(PPhMe2)(2)] (2), trans-[PtCl(sac)(PPh2Et)(2)] (3) and trans- [PtCl(sac) (PPhEt2)(2)] (4) complexes (sac = saccharinate) were synthesized and characterized by elemental analysis and spectroscopic methods. The structures of 2-4 were determined by X-ray single-crystal diffraction. The interaction of the complexes with DNA was studied various biochemical, biophysical and molecular docking methods. Only the cis-configured complexes (1 and 2) showed nuclease activity and their binding affinity towards DNA was considerably higher than those of their trans-congeners (3 and 4). The chlorido ligand in the cis-configured complexes underwent aquation, making them more reactive towards DNA. Furthermore, 1 and 2 exhibited anticancer potency on breast (MCF-7) and colon (HCT116) cancer cells similar to cisplatin, whereas 3 and 4 were biologicallly inactive. Mechanistic studies on MCF-7 cells showed that higher nuclear uptake, cell cycle arrest at the S phase, dramatically increased DNA double-strand breaks, apoptosis induction, elevated levels of reactive oxygen species (ROS) and high mitochondrial membrane depolarization greatly contribute to the anticancer potency of 1 and 2.