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

[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 = PdII (1, 3 and 5) and PtII (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/HSA 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 mitochondrial depolarization and DNA damage. [Display omitted] •New Pd(II)/Pt(II) saccharinate complexes of bis(diphenylphosphino)propane/butane were synthesized.•Cationic complexes (3 and 4) showed excellent antiproliferative activity.•The neutral complex (6) was highly cytotoxic activity of against A549 and HCT116 cells.•Complex 6 blocked the cell cycle progression at the S phase.•Complex 6 induced apoptosis through ROS-mediated mitochondrial and DNA damage.