Anticancer activity and cell death mechanism of Pt(II) complexes: Their in vitro bio-transformation to Pt(II)-DNA adduct formation and BSA binding study by spectroscopic method

Synthesis and spectroscopic characterization of cytotoxic Pt(II) complexes with PEA carrier ligand followed by in vitro BSA transported drug delivery. The complexes are less toxic and more effective on different cancer cell lines. [Display omitted] •Pt(II) complexes with PEA carrier ligand and different biomolecules have been synthesised and well characterized by multi-spectroscopic methods.•The complexes bind with CT-DNA and BSA in a good extent, supported by spectroscopic results and molecular docking study with BDNA.•H- bonding and van der Waals forces are the operating forces for the sponteneous association between BSA/Pt(II) complexes.•Pt(II) complexes prompted better IC50 values in A549 and HEp-2 cancer cell lines, over the recognized anticancer drugs and less toxic towards nornal cell L6 myotubes.•The cell death mechanism on HEp-2 reveals the crucial role of complexes in phase population. Pt(II) complex cis-[Pt(PEA)(OH2)2] X2, C-2 (where, PEA = 2-Pyridylethylamine and X = ClO4− or NO3–) was synthesized by hydrolysis of cis-[Pt(PEA)Cl2] C-1. Glutathione (GSH) and DL-penicilamine (DL-pen) substituted complexes cis-[Pt(PEA)(GSH)],C-3 and cis-[Pt(PEA)DL-pen)]X C-4 were synthesized and characterized by spectroscopic methods. Kinetic studies were traced on complex C-2 with the thiols, GSH and DL-pen. Pt(II)-Sulfur adduct formation mechanisms of the substituted products C-3 and C-4 were established from the kinetic investigation. At pH 4.0, C-2 - thiols interactions follow two consecutive steps: the first step is dependent, and the second is independent of [thiol]. The association equilibrium constant (KE), substitution rate constants for both steps (k1 & k2), and activation parameters (ΔH‡ and ΔS‡) have been assessed to propose the mechanism. Agarose gel electrophoresis mobilization pattern of DNA with complexes was performed to visualize the interaction nature. CT-DNA and BSA binding activities of the complexes have been executed by electronic, fluorescence spectroscopy, and viscometric titration methods. Evaluation of thermodynamic parameters (ΔH0, ΔS0, and ΔG0) from BSA binding constants was executed to propose the driving forces of interaction between these species. A molecular docking study was performed to evaluate the binding mode of complexes with BDNA strands. Anticancer activity of the complexes C-1 to C-4 was explored on both A549 and HEp-2 cell lines, compared with approved anticancer drugs cisplatin, carboplatin, and oxaliplatin. All these c