Photophysical study on DNA & BSA binding and cytotoxic behaviour of piperidine-Pt(II) complexes: Their kinetics & mechanism and molecular docking

[Display omitted] •Pt(II) complexes with piperidine derivative as carrier ligand and sulfur containing amino acids as leaving group have been synthesized and well characterized by spectroscopic method, thermal analysis and TDDFT simulation.•The Pt(II) complexes bind with CT -DNA in good extend which are comparable with recognized drugs and supported by molecular docking with BDNA.•Hydrogen bonding and van der Waals forces are the operating forces between Pt(II) complexes and BSA, supported by spectroscopic method and molecular docking with 4F5S.•The Pt(II) complexes are cytotoxic to MCF 7, A549, and HCT 116 but better effect is shown on MCF 7 cells, similar to recognized drugs and moderately less toxic to normal cell HEK 293.•The profound ROS generated on MCF 7 cells by the complexes and the cell cycle analysis reveals the effect of Pt(II) complexes on cell population in different phases. For the development of Pt(II) based anticancer drug candidates, carrier ligand 2-(Piperidine-1-yl)ethylamine (PIEAM) was used as a bidentate chelator to synthesize dichloro complex [Pt(PIEAM)Cl2] C-1 and its diaqua [Pt(PIEAM)(OH2)2](X)2 (C-2). The diaqua complex C-2 was further used to synthesize thiol substituted Pt(II)-sulfur complexes with l-cysteine (LC) and N-acetyl-l-cysteine (NAC). The Pt(II) complexes were characterized by multi spectroscopic methods and thermal analysis. The role of electronic and steric factors of carrier ligand PIEAM on substitution reactions of C-2 with LC and NAC was studied in aqueous medium at pH 4.0 under pseudo first-order kinetics and rate constant, equilibrium constant and thermodynamic parameters were calculated. The DNA binding activity and binding mode were confirmed by gel electrophoresis and viscosity measurement. The binding activity of Pt(II) complexes with DNA and BSA was explored by absorption and fluorometric titration methods. In vitro MTT assay of Pt(II) complexes were tested on different cancer cell lines like; MCF 7, A549, HCT 116 and also on normal human embryonic kidney cell HEK 293. The cell cycle arrest of MCF 7 cell growth and also the oxidative stress level (ROS) after treating with Pt(II) complexes were analysed. The structural optimization for molecular docking of Pt(II) complexes at B3LYP functional level were performed to correlate the experimental findings. The antineoplastic activity and drug likeness behaviour of Pt(II) complexes were further supported by PASS prediction and in silico ADME analysis.