Oxidative Assets Toward Biomolecules and Cytotoxicity of New Oxindolimine-Copper(II) and Zinc(II) Complexes

Abstract

A new oxindolimine ligand derived from isatin (1H-indole-2,3-dione) and 2-aminomethylbenzimidazole was synthesized, leading to two novel complexes after metalation with copper(II) perchlorate or zinc(II) chloride, [Cu(isambz)2](ClO4)2 (complex 1) and [Zn(isambz)Cl2] (complex 2). This new ligand was designed as a more lipophilic compound, in a series of oxindolimine–metal complexes with antitumor properties, having DNA, mitochondria, and some proteins, such as CDK1 kinase and topoisomerase IB, as key targets. The new complexes had their reactivity to human serum albumin (HSA) and DNA, and their cytotoxicity toward tumor cells investigated. The binding to CT-DNA was monitored by circular dichroism (CD) spectroscopy and fluorescence measurements using ethidium bromide in a competitive assay. Consequent DNA cleavage was verified by gel electrophoresis with complex 1, in nmolar concentrations, with formation of linear DNA (form III) after 60 min incubation at 37 °C, in the presence of hydrogen peroxide, which acts as a reducing agent. Formation of reactive oxygen species (ROS) was observed, monitored by spin trapping EPR. Interaction with HSA lead to α-helix structure disturbance, and formation of a stable radical species (HSA–Tyr·) and carbonyl groups in the protein. Despite showing oxidative ability to damage vital biomolecules such as HSA and DNA, these new complexes showed moderate cytotoxicity against hepatocellular carcinoma (HepG2) and neuroblastoma (SHSY5Y) cells, similarly to previous compounds in this series. These results confirm DNA as an important target for these compounds, and additionally indicate that oxidative damage is not the leading mechanism responsible for their cytotoxicity. Additionally, this work emphasizes the importance of ligand characteristics and of speciation in activity of metal complexes.

One-Pot Surface Modification of β-Cu2O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

“…DPPH radicals have shown an absorption maximum of purple coloration at a wavelength of 517 nm and turn yellow when it accepts an electron. Discoloration of DPPH started after adding the β-Cu 2 O NPs due to antioxidant ability, and the radical scavenging ability increases with an increase in concentration from 15 to 60 μg/mL in the percentage inhibition ranging from 38 ± 5 to 83 ± 5% (Figure ). The increase in concentration successively exhibited the highest percentage inhibition…”

Degradation of Human Serum Albumin by Infrared Free Electron Laser Enhanced by Inclusion of a Salen-Type Schiff Base Zn (II) Complex

“…In recent years, researches on artificial metalloenzymes, namely, docking metal complexes to proteins, such as bio-inspired catalysts, drug discovery, and biofuel cells have attracted increased attention [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Because certain proteins can deliver drugs to anticancer cells, experiments to dock with nucleic acids, as well as proteins, have also been widely performed.…”

Unconventional Anticancer Metallodrugs and Strategies to Improve Their Pharmacological Profile

“…This Special Issue also collects reports on the synthesis and anticancer properties of compounds containing metals other than platinum [16][17][18][19][20]. Navarro et al report cell viability assays on selected human cancer cell lines of cationic ruthenium(II) compounds based on p-cymene, triphenylphosphine, and biologically active clotrimazole and ketoconazole as ligands [16].…”

“…Preliminary studies on the cell cycle and mechanism of cell death as well as the promising anti-migration activity of a selected compound with clotrimazole on a triple negative breast tumor cancer cell line were reported [16]. Da Costa Ferreira et al contributed to this issue with a report on new copper(II) and zinc(II) complexes containing new oxindolimine ligands [17]. The cytotoxicity of these compounds against hepatocellular carcinoma and neuroblastoma cancer cell lines, as well as their reactivity toward Calf Thymus DNA and human serum albumin, was investigated.…”

“…The cytotoxicity of these compounds against hepatocellular carcinoma and neuroblastoma cancer cell lines, as well as their reactivity toward Calf Thymus DNA and human serum albumin, was investigated. The main conclusion is a confirmation of DNA as an important target for these compounds and an indication that oxidative damage is not the leading mechanism of cell death [17]. Three other leading medicinal inorganic chemistry groups contributed original articles on gold compounds [18][19][20].…”