Synthesis, characterization and anticancer activities of transition metal complexes with a nicotinohydrazone ligand

Abstract

Abstract. The reaction of divalent transition metal salts and (E)-N'-(1-(pyridin-2-yl)ethylidene)nicotinohydrazide (penh) led to the formation of [Mn(penh) 2 ] (complex 1), [Co(penh) 2 ] (complex 2), [Cu(penh) 2 ] (complex 3) and [Cd (penh) 2 ] (complex 4) complexes. The four complexes were characterized using elemental analyses, infrared spectra and single-crystal X-ray diffraction analyses. Subsequently, the complexes were used for in vitro cell level experiments to determine potential antitumor effects. The results demonstrated that the complexes exhibited a similar structure; however, they were crystallized with distinct space groups. In comparison with the uncomplexed penh ligand, all four complexes were able to markedly decrease the proliferation rate of various types of tumor cell, including the human lung cancer cell line A549, human gastric cancer cell line BGC823 and human esophageal cancer cell line Eca109, in a concentration-dependent manner. Furthermore, the complexes promoted tumor cell apoptosis, as demonstrated in the apoptosis assay, and this was confirmed using electrophoresis. IntroductionHydrazide-hydrazone derivatives are an important class of biologically active molecules, which have attracted the attention of medicinal chemists due to their wide-ranging pharmacological properties and their potential application as antitumor, antineoplastic, antiviral and anti-inflammatory agents (1-6).In particular, aroylhydrazone complexes of transition metals are known to provide useful models for the elucidation of the underlying molecular mechanism of enzyme inhibition by hydrazine derivatives (7) and for their potential pharmacological application (8,9). Hydrazone derivatives of isoniazid and other hydrazides have been reported to exhibit marked antimicrobial activity (10-14). Furthermore, a number of substituted hydrazone derivatives have been synthesized and evaluated for their antitumor activity, with certain promising results having been reported (15-17).The aim of the present study was to develop potent anticancer agents. (E)-N'-(1-(pyridin-2-yl)ethylidene) nicotinohydrazide (penh), and [Mn(penh) 2 ] (complex 1), [Co (penh) 2 ] (complex 2), [Cu(penh) 2 ] (complex 3) and [Cd(penh) 2 ] (complex 4) metal complexes were synthesized, and their cytotoxicity against human lung cancer (A549), human gastric cancer (BGC823) and human esophageal cancer (Eca109) cell lines was investigated. Materials and methodsMaterials. All starting materials were obtained commercially and used as received. The A549 human lung cancer, BGC823 human gastric cancer and Eca109 human esophageal cancer cell lines were obtained from the Cell Culture Center of the Basic Institute of Medical Sciences (Peking Union Medical College, Beijing, China). Cell culture reagents were purchased from Gibco (Thermo Fisher Scientific, Inc., Waltham, MA, USA). An Annexin V/propidium iodide (PI) double staining kit was purchased from BD Biosciences (Franklin Lakes, NJ, USA). MTT and dimethyl sulfoxide (DMSO) were purchased from Sigma-Aldrich (Merc...

Schiff Base Metal Complexes as Anticancer Agents

“…Shen et al [41] reported the synthesis and characterization of divalent transition metal complexes e.g., Co(II), Cu(II), Cd(II) and Mn(II) with nicotinohydrazide ligand. The complex also used for in vitro cell experiment to test the antitumour effect.…”

“…The results revealed that the uncomplexed ligand show cytotoxic effect than the metal complexes. Metal complexes can effectively decrease the proliferation rate of different type of cancerous cell line like human gastric cancer cells, human esophageal cancer cell line (ECA109) in a dose dependent manner [41].…”

Fabrication of novel Fe (III), Co (II), Hg (II), and Pd (II) complexes based on water‐soluble ligand (NaH2PH): structural characterization, cyclic voltammetric, powder X‐ray diffraction, zeta potential, and biological studies

“…The results that obtained the metal complexes have significant ability to inhibit cancer cell proliferation, and that the effect is higher than the free ligand (NaH 2 PH), which proposed that the chelated transition metal in the complex plays essential role in enhancing the complex activities. [ 55 ] The Hg (II) complex displayed the highest anticancer activities against liver cancer (HePG‐2) and breast cancer (MCF‐7) cell lines. It means that the chemical structure of the examined compounds play an important role in the biological properties and produce a new anticancer drug.…”

Synthesis of a new Cd (II) complex as ionophores and its application in construction of a highly selective and sensitive cadmium (II) sensor in petroleum water samples

“…This indicates that improving the activities of transition metals depends critically on their coordination. 63 This activity is based on their ability to bind DNA, which causes them to damage or modify their structure, decreasing their ability to perform their role. 25 According of the results, the complex has the potential to be used as a promising anticancer drug in vivo to halt the DNA replication in the cancer cells and to stop the growth of the tumor.…”