Synthesis, Structural Investigations, Molecular Docking, and Anticancer Activity of Some Novel Schiff Bases and Their Uranyl Complexes

Biomolecules. 2021 Aug 2;11(8):1138. doi: 10.3390/biom11081138.


Three novel 2-aminopyrazine Schiff bases derived from salicylaldehyde derivatives and their uranyl complexes were synthesized and characterized by elemental analysis, UV-vis, FTIR, molar conductance, and thermal gravimetric analysis (TGA). The proposed structures were optimized using density functional theory (DFT/B3LYP) and 6-311G ∗(d,p) basis sets. All uranyl complexes are soluble in DMSO and have low molar conductance, which indicates that all the complexes are nonelectrolytes. The DNA binding of those Schiff bases and their uranyl complexes was studied using UV-vis spectroscopy, and screening of their ability to bind to calf thymus DNA (CT-DNA) showed that the complexes interact with CT-DNA through an intercalation mode, for which the Kb values ranged from 1 × 106 to 3.33 × 105 M-1. The anticancer activities of the Schiff base ligands and their uranyl complexes against two ovarian (Ovcar-3) and melanoma cell lines (M14) were investigated, and the results indicated that uranyl complexes exhibit better results than the Schiff base ligands. Molecular docking identified the distance, energy account, type, and position of links contributing to the interactions between these complexes and two different cancer proteins (3W2S and 2OPZ).

Keywords: DFT; DNA binding; Schiff base; anticancer; molecular docking; uranyl complexes.

MeSH terms

  • Aldehydes / chemistry
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Cattle
  • Cell Line, Tumor
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / metabolism
  • Coordination Complexes / pharmacology
  • DNA / chemistry
  • DNA / metabolism
  • Density Functional Theory
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • ErbB Receptors / chemistry
  • ErbB Receptors / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Intercalating Agents / chemical synthesis*
  • Intercalating Agents / metabolism
  • Intercalating Agents / pharmacology
  • Kinetics
  • Molecular Docking Simulation
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • Pyrazines / chemistry
  • Schiff Bases / chemical synthesis*
  • Schiff Bases / metabolism
  • Schiff Bases / pharmacology
  • Solubility
  • Uranium Compounds / chemistry
  • X-Linked Inhibitor of Apoptosis Protein / chemistry*
  • X-Linked Inhibitor of Apoptosis Protein / metabolism


  • Aldehydes
  • Antineoplastic Agents
  • Coordination Complexes
  • Intercalating Agents
  • Pyrazines
  • Schiff Bases
  • Uranium Compounds
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • salicylaldehyde
  • DNA
  • calf thymus DNA
  • EGFR protein, human
  • ErbB Receptors