Synthesis, characterization, crystal structure, and molecular docking of o-vanillin and l-valine derived molecules: a DFT study and antiproliferative activity against the PANC-1 cancer cell line

Abstract

Cu(II) complexes 1 and 2 with and without a coligand (2,2′-bipyridyl) were synthesized using the ligand NaLH = 2-{(E)-[(2-hydroxy-3-methoxyphenyl)methylidene]amino}-3-methylbutanoic acid, which was prepared from o-vanillin and L-valine. ¹H-NMR, UV-vis, and FTIR techniques were used to characterize the molecules, while DFT and single crystal XRD techniques predicted the octahedral geometry of complex 1 and square pyramidal geometry of complex 2 (with a coligand). The DFT-B3LYP method was used to compute HOMO and LUMO frontier orbitals, band gaps, and geometry optimization of the complexes. The Cu(II) complex with the coligand has shown a lower energy gap. The DNA binding studies revealed an intercalative mode of binding of complexes with CT DNA and they also effectively cleaved the genomic DNA in nuclease activity analysis with binding constants of 2.3 × 10⁵ M⁻¹ to 4.2 × 10⁵ M⁻¹. Complex 2 has shown remarkable binding affinity with −10.82 kcal mol⁻¹ and −11.97 kcal mol⁻¹ binding energies in the molecular docking study against EGFR kinase and TRK receptor molecules. The IC₅₀ values of 8 μM, 4.1 μM and 2.8 μM for the ligand and complexes 1 and 2, respectively, were found against PANC-1 cancer cells in cell viability assays. However, 1 and 2 displayed 80% to 72.84% cell viability of human normal pancreatic cells at different concentrations. Furthermore, the cell cycle results also confirmed that 1 and 2 arrested the PANC-1 cells in the G2M phase of the cell cycle followed by an increase in the sub-G1 phase. These results indicated that 1 and 2 are potent anticancer complexes against PANC-1 cancer cell lines.