Synthesis of Carbazole-Substituted thiosemicarbazone and its Cu(II) Complex, DNA/Protein Binding, Cytotoxic, antiproliferative activities and molecular docking studies


Findik M., Kuzu B., Pehlivanoglu S., Kaya S., Sayin U., Guler Akgemci E., ...More

Inorganic Chemistry Communications, vol.152, 2023 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 152
  • Publication Date: 2023
  • Doi Number: 10.1016/j.inoche.2023.110711
  • Journal Name: Inorganic Chemistry Communications
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, DIALNET
  • Keywords: Antiproliferative activity, Cu(II) complex of thiosemicarbazone, Cytotoxicity, DNA/BSA interaction, EPR, Molecular docking, Ovarian cancer, TD-DFT
  • Van Yüzüncü Yıl University Affiliated: Yes

Abstract

In this study, 9-ethyl-3-carbazolecarboxaldehyde-4-ethyl-thiosemicarbazone (ECCAET) and its copper(II) complex (Cu(ECCAET)2) were firstly synthesized and characterized. DFT and EPR studies confirmed that the complex is mononuclear and has square planar geometry. The interaction of all synthesized compounds with calf thymus DNA (CT-DNA) was examined by absorption and fluorescent spectroscopy. The experimental results showed that Cu(ECCAET)2 interacts with DNA via an intercalative binding mode. The binding interactions of the complex with CT-DNA have been confirmed through viscosity measurements revealing that the complex interacts with DNA via intercalation. Furthermore, the protein binding ability of ECCAET and Cu(ECCAET)2 was investigated using BSA via electronic absorption spectral titration, fluorescence quenching, and synchronous fluorescence spectrum studies, which revealed that the Cu(ECCAET)2 strongly bound to BSA over the ligand. Molecular docking studies were also performed to support the bonding mechanism of ECCAET and Cu(ECCAET)2 with DNA and BSA. The biological activity studies of ECCAET and Cu(ECCAET)2 against cancer cells were also investigated. A panel of cancer cell lines, including A2780 human ovarian adenocarcinoma, MDA-MB-231 human triple-negative breast adenocarcinoma, and as a control non-cancerous L929 fibroblast cell lines were also used to test the compounds' anticancer activities. Cytotoxic and antiproliferative properties of Cu(ECCAET)2 were visibly higher than its ligand (ECCAET) for all tested cell lines. The Cu(ECCAET)2 had a distinctive biological effects on A2780, and MDA-MB-231 cells compared to non-cancerous cells. Within these results, Cu(ECCAET)2 was found a promising drug candidate against gynecologic cancer diseases.