DNA/BSA binding affinity studies of new Pd(II) complex with S-S and N-N donor mixed ligands via experimental insight and molecular simulation: Preliminary antitumor activity, lipophilicity and DFT perspective

Due to the importance of metallo drugs that can bind to DNA and prohibit division of cancer cells, a novel water-like palladium(II) complex, [Pd(phen)(proli-dtc)]NO3 (phen = 1,10-phenanthroline and proli-dtc = pyrrolinedithiocarbamate), has been prepared in this work. The structure of this metal complex was verified utilizing experimental and computational analysis. The central Pd(II) ion was found to be at the center of a square-planar arrangement. The preliminary antitumor activity and lipophilicity of the compound was more impressive than that of cisplatin. Moreover, in silico prediction demonstrated that this complex has low toxicity effects and possesses high drug-likeness. DFT calculations were conducted to study the reactivity and stability descriptors as well as NBO analysis of the mentioned complex. The binding affinity of Pd(II) complex to CT-DNA was explored utilizing fluorescence, electronic absorption spectroscopy, gel electrophoresis and viscosity test which illustrated that this complex could strongly interact with CT-DNA through hydrophobic interaction (intercalation mode). In addition, the interaction between complex and BSA was investigated by fluorescence, electronic absorption, CD spectroscopy and FRET analysis and the obtained findings illustrated a moderate interaction in BSA-Pd (II) complex system via hydrogen bond and van der Waals forces. The results of electronic absorption and CD spectra exhibited that the complex refolded the BSA by increasing the percentage of alpha-helix. Docking simulation was also performed to predict the binding pose of the metal complex to both biomolecules. (C) 2021 Elsevier B.V. All rights reserved.