A novel palladium(II) antitumor agent: Synthesis, characterization, DFT perspective, CT-DNA and BSA interaction studies via in-vitro and in-silico approaches

Since numerous people annually pass away due to cancer, research in this field is essential. Thus a newly made and water like palladium(II) complex of formula [Pd(phen)(acac)]NO3, where phen is 1,10-phenanthroline and acac is acetylacetonato ligand, has been synthesized by the reaction between [Pd(phen)(H2O)(2)](NO3)(2) and sodium salt of acetylacetone in the molar ratio of 1:1. It has been structurally characterized via the methods such as conductivity measurement, elemental analysis and spectroscopic methods (FT-IR, UV-Vis and H-1 NMR). The geometry optimization of this complex at the DFT level of theory reveals that Pd(II) atom is situated in a square-planar geometry. The complex has been screened for its antitumor activity against K562 cancer cells which demonstrated efficacious activity. The interaction of above palladium(II) complex with CT-DNA as a target molecule for antitumor agents and BSA as a transport protein was studies by a variety of techniques. The results of UV-Vis absorption and fluorescence emission indicated that the Pd(II) complex interacts with EB + CT-DNA through hydrophobic and with BSA by hydrogen bonding and van der Waals forces at very low concentrations. In these processes, the fluorescence quenching mechanism of both the macromolecules seems to be the combined dynamic and static. The interaction was further supported for CT-DNA by carrying out the gel electrophoresis and viscosity measurement and for BSA by the circular dichroism and Forster resonance energy transfer experiments. Furthermore, results of partition coefficient determination showed that the [Pd(phen)(acac)]NO3 complex is more lipophilic than that of cisplatin. Moreover, molecular docking simulation confirms the obtained results from experimental tests and reveals that the complex tends to be located at the intercalation site of DNA and Sudlow's site I of BSA. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

The newly synthesized palladium(II) complex exhibits significant anti-tumor activity and interacts with CT-DNA and BSA through hydrophobic interactions with CT-DNA, and hydrogen bonding and van der Waals forces with BSA. Additionally, partition coefficient determination shows that [Pd(phen)(acac)]NO3 complex is more lipophilic than cisplatin. Molecular docking simulation confirms experimental results and suggests the complex binds to the intercalation site of DNA and Sudlow's site I of BSA.