Synthesis, anti-tumour activity, and mechanism of benzoyl hydrazine Schiff base-copper complexes

Abstract

Four new complexes of Cu(II) coordinated to a benzoyl hydrazine Schiff base–[Cu(L1)Cl] (C1), [Cu(L1)Py] (C2), [Cu(L2)NO3] (C3), [Cu(L3)NO3] (C4)– were synthesized and characterized. X-ray crystallography results indicated that all complexes had four-coordinated copper centers. The molecular structures of the complexes were altered by linking the phenyl or pyridyl group with the ligand branch or by attaching a second ligand (Py, pyridine) to the copper center. The IC50 values of the four complexes acting on the selected tumour cells were 2.69–16.32 µM. The C1 and C2 complexes could up-regulate the expression of p21 in order to down-regulate the expression of cyclin D1, cyclin E, and CDK2, which caused the cell cycle to be arrested in the G1 phase. Further studies revealed that the C2 complex was able to stabilize G-quadruplex (G4) DNA structure, including that of the proto-oncogene c-kit and the Pu27 sequence situating the promoter region of c-myc, which led to the significant inhibition the expression of c-myc and c-kit. This affected the expression of downstream proteins, such as hTERT and Bcl-2, ultimately inducing apoptosis.