Novel P,C-orthopalladated complexes containing histidine and phenylalanine amino acids: synthesis, DNA and BSA interactions, in vitro antitumoral activity and molecular docking approach

Novel [Pd(o-CH2C6H4P(o-tolyl)(2))(histidine)] (1) and [Pd(o-CH2C6H4P(o tolyl)(2))(phenylalanine)] (2) P,C-orthopalladated complexes have been prepared and characterized by elemental analysis, IR and NMR spectroscopy. To study the stability of the compounds in biological media, the complexes were incubated in Tris buffer during 10 days. The absorbance of the compounds remained constant, which confirmed the stability of the complexes in biological media. UV-Vis absorption spectrophotometry, fluorescence spectroscopy and viscosity studies were used to investigate the binding of the complexes with native calf thymus DNA (CT-DNA). These methods along with competitive binding of methylene blue (MB) DNA show that the complexes interact with DNA via groove mode. The UV-Vis absorption spectrophotometry of BSA with complexes has shown an alpha-helix perturbation induced by a particular interaction between the metal complexes and BSA. In addition, the fluorescence quenching mechanism of BSA with the complexes is a static process, according to the fluorescence spectrometry of bovine serum albumin (BSA). The experimental results of site competitive replacement with specific site markers are clear indications that the complexes bind to site I of BSA. Furthermore, both complexes showed significant selective cytotoxic activity against melanoma B16F0 and colon carcinoma C26 cancer cells as well as normal fibroblast NIH cell line. Ultimately, the binding of Pd(II) complexes to DNA and BSA was verified by molecular docking experiment. Communicated by Ramaswamy H. Sarma

Automated summary

Novel Pd(II) complexes were prepared and characterized. The stability of the complexes in biological media was confirmed, and their interaction with DNA and BSA was investigated. The complexes showed selectivity against cancer cells and binding to specific sites of BSA.