Pd(II) and Pt(II) saccharinate complexes of bis(diphenylphosphino) propane/butane: Synthesis, structure, antiproliferative activity and mechanism of action


YILMAZ V. T. , İÇSEL C. , AYGÜN M., Erkisa M., Ulukaya E.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol.158, pp.534-547, 2018 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 158
  • Publication Date: 2018
  • Doi Number: 10.1016/j.ejmech.2018.09.035
  • Title of Journal : EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Page Numbers: pp.534-547
  • Keywords: Pd(II) and Pt(II), Saccharinate, Bis(diphenylphosphino)propane/butane, A549 lung cancer cell, HCT116 colon cancer cell, Anticancer mechanism, CELLS IN-VITRO, THIOSACCHARINATE TSAC COMPLEXES, ASCITES-CARCINOMA EAC, DOUBLE-STRAND BREAKS, DNA-BINDING AGENTS, PLATINUM(II) COMPLEXES, CRYSTAL-STRUCTURES, MOLECULAR-STRUCTURES, PALLADIUM COMPLEXES, ANTICANCER ACTIVITY

Abstract

[M(sac)(2)(dppp)] (1 and 2), [M(dppp)(2)](sac)(2) (3 and 4) and [M(sac)(2)(dppb)] (5 and 6) complexes, where M = Pd-II (1, 3 and 5) and Pt-II (2, 4 and 6), sac = saccharinate, dppp = 1,3-bis(diphenylphosphino)propane and dppb = 1,4-bis(diphenylphosphino)butane, were synthesized and characterized by IR, NMR, ESI-MS and X-ray diffraction. The anticancer activity of the complexes against human lung (A549), breast (MCF-7), prostate (DU145) and colon (HCT116) cancer cell lines showed that the cationic complexes of dppp (3 and 4) and neutral Pt complex of dppb (6) were the most active agents of series. 3 and 4 exhibited antiproliferative activity, while 6 was highly cytotoxic compared to cisplatin. These complexes were therefore subjected to further investigations to ascertain the possible role of lipophilicity, cellular uptake and DNA/EISA binding in their biological activity. Flow cytometry analysis revealed that complex 6 induced apoptotic cell death in A549 and HCT116 cells and caused the cell cycle arrest at the S phase and overproduction of reactive oxygen species (ROS), giving rise to mitochondria) depolarization and DNA damage. (C) 2018 Elsevier Masson SAS. All rights reserved.