Novel transition metal (II) complexes of hydrazones as potential antitumor agents: Synthesis, characterization, DFT computations, cytotoxic activities, molecular docking and simulation studies

Abstract

In this study, novel Cu(II), Co(II), and Fe(II) metal complexes comprising pyridine-based hydrazone ligands (L<inf>1</inf> and L<inf>2</inf>) and their new mixed-ligand metal complexes with 1,10-phenanthroline (phen) were also prepared. The complexes were characterized by molar conductivity measurements, magnetic susceptibility, elemental analysis, fourier-transform infrared (FT-IR), mass, and Ultraviolet-visible (UV–Vis) spectroscopy. All the synthesized complexes were assessed in human lung (A549) and human liver cancer (HepG2) cell lines. In particular, two of the synthesized complexes, [Cu(L<inf>1</inf>)(phen)(OAc)<inf>2</inf>].3H<inf>2</inf>O (4) and [Cu(L<inf>2</inf>)(phen)(OAc)<inf>2</inf>].3H<inf>2</inf>O (10), exhibited a significantly elevated antiproliferative impact, demonstrating almost two and a half times greater efficacy in the A549 cell line and twenty times more effectiveness in the liver cancer cell line compared to the positive control drug cisplatin. Copper chelate complexes exhibited the highest level of activity in the in vitro activity analysis. The probable mechanism of action of the active ligand, copper chelate complexes, in this investigation was examined using molecular modeling. The binding affinity of the 4 and 10 copper chelate complexes to the nucleotide binding domain 1 (NBD1) of MRP1 was analyzed via molecular docking. The stability of the protein-ligand chelate complexes obtained from docking was investigated using molecular dynamics (MD) simulations. © 2025 Elsevier B.V., All rights reserved.