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

IF 2.7 3区化学 Q2 CHEMISTRY, INORGANIC & NUCLEAR

Inorganica Chimica Acta Pub Date : 2025-03-07 DOI:10.1016/j.ica.2025.122634

Hatice Gamze Sogukomerogullari , Eyüp Başaran , Reşit Çakmak , Muhammed Tılahun Muhammed , Senem Akkoc

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引用次数: 0

Abstract

In this study, novel Cu(II), Co(II), and Fe(II) metal complexes comprising pyridine-based hydrazone ligands (L₁ and L₂) 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(L₁)(phen)(OAc)₂].3H₂O (4) and [Cu(L₂)(phen)(OAc)₂].3H₂O (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.

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来源期刊

Inorganica Chimica Acta 化学-无机化学与核化学

CiteScore

6.00

自引率

3.60%

发文量

440

审稿时长

35 days

期刊介绍： Inorganica Chimica Acta is an established international forum for all aspects of advanced Inorganic Chemistry. Original papers of high scientific level and interest are published in the form of Articles and Reviews. Topics covered include: • chemistry of the main group elements and the d- and f-block metals, including the synthesis, characterization and reactivity of coordination, organometallic, biomimetic, supramolecular coordination compounds, including associated computational studies; • synthesis, physico-chemical properties, applications of molecule-based nano-scaled clusters and nanomaterials designed using the principles of coordination chemistry, as well as coordination polymers (CPs), metal-organic frameworks (MOFs), metal-organic polyhedra (MPOs); • reaction mechanisms and physico-chemical investigations computational studies of metalloenzymes and their models; • applications of inorganic compounds, metallodrugs and molecule-based materials. Papers composed primarily of structural reports will typically not be considered for publication.