New thiosemicarbazone-based Zinc(II) complexes. In vitro cytotoxicity competing with cisplatin on malignant melanoma A375 cells and its relation to neuraminidase inhibition

Chem Biol Interact. 2022 Jan 5:351:109757. doi: 10.1016/j.cbi.2021.109757. Epub 2021 Nov 27.

Abstract

New thiosemicarbazone-based zinc(II) complexes were synthesized to study their cytotoxicity on A375 malignant melanoma cells. The complexes containing salicylidene (Zn1a), 3-methoxy-salicylidene (Zn1b) or 4-methoxy-salicylidene (Zn1c) moiety were characterized by analytical and spectroscopic methods. Anticancer potential of the complexes was determined by MTT test and HUVEC endothelial cells line was used to comprehend the effect on normal cells. Zn1b with an IC50 of 13 μM was found to be highly cytotoxic against A375 cancer cells, more effective than cisplatin (IC50: 37 μM). Zn1a and Zn1c did not have a negative effect on cell viability in the normal cells and gave the impression that they are more advantageous than cisplatin in this respect. Further, the ability of Zn1a-c to inhibit neuraminidase enzyme and its role in cytotoxicity was discussed. The test revealed that the Zn1b with 3-methoxy substituent exhibited higher inhibition activity against the neuraminidase than the Zn1a and Zn1c as analogical to the cytotoxicity results. In neuraminidase inhibition, IC50 values of Zn1b and Zn1c were 14 and 66 μM, respectively. These concentrations were very close to the cytotoxicity concentrations for Zn1b and Zn1c. The findings may indicate the role of neuraminidase enzyme inhibition in cell death for Zn1b and Zn1c.

Keywords: Anticancer activity; Neuraminidase; Thiosemicarbazone; Zinc complexes.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / pharmacology*
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / pharmacology*
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Molecular Structure
  • Neuraminidase / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Thiosemicarbazones / chemical synthesis
  • Thiosemicarbazones / pharmacology*
  • Zinc / chemistry

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Enzyme Inhibitors
  • Thiosemicarbazones
  • Neuraminidase
  • Zinc
  • Cisplatin