Two hydrazone copper(ii) complexes: synthesis, crystal structure, cytotoxicity, and action mechanism

Abstract

Two copper(II) complexes with 8-quinolinecarbaldehyde o-vanilloylhydrazone (H-L1) and 8-quinolinecarbaldehyde salicylhydrazone (H-L2), [Cu(L1)NO₃] (1) and [Cu(L2)NO₃] (2), were synthesized and structurally characterized, respectively. Complexes 1 and 2 exhibited enhanced cytotoxicity against BEL-7402, Hep-G2, NCI-H460, MGC80-3, HeLa tumor cells compared with free ligands and copper(II) salt and slightly lower than that shown by cisplatin. And MGC80-3 cells are more sensitive to these two complexes relative to the normal liver cells. Cytotoxicity and action mechanism studies suggest 1 and 2 could cause MGC80-3 cell cycle arrest at G1 phase, which is induced by limiting the supply of cyclins D1 and E1 and inhibiting the activity of G1-phase-promoting cyclin–Cdk complexes. And complexes 1 and 2 led to cell apoptosis via the activation of Bcl-2 protein. Moreover, mitochondrial dysfunction was induced by both of complexes.