Diselenides and Benzisoselenazolones as Antiproliferative Agents and Glutathione-S-Transferase Inhibitors

Molecules. 2019 Aug 11;24(16):2914. doi: 10.3390/molecules24162914.

Abstract

A series of variously functionalized selenium-containing compounds were purposely synthesized and evaluated against a panel of cancer cell lines. Most of the compounds showed an interesting cytotoxicity profile with compound 5 showing a potent activity on MCF7 cells. The ethyl amino derivative 5 acts synergistically with cis-platin and inhibits the GST enzyme with a potency that well correlates with the cytotoxicity observed in MCF7 cells. A computational analysis suggests a possible binding mode on the GST enzyme. As the main outcome of the present study, the ethyl amino derivative 5 emerged as a valid lead compound for further, future developments.

Keywords: benzisoselenazolone; breast cancer; diselenide; glutathione S-transferase.

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Proliferation / drug effects*
  • Cytotoxins / chemical synthesis
  • Cytotoxins / chemistry
  • Cytotoxins / pharmacology
  • Enzyme Inhibitors* / chemical synthesis
  • Enzyme Inhibitors* / chemistry
  • Enzyme Inhibitors* / pharmacology
  • Glutathione Transferase / antagonists & inhibitors*
  • Glutathione Transferase / metabolism
  • HeLa Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • K562 Cells
  • MCF-7 Cells
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / metabolism
  • Organoselenium Compounds* / chemical synthesis
  • Organoselenium Compounds* / chemistry
  • Organoselenium Compounds* / pharmacology
  • Selenium Compounds* / chemical synthesis
  • Selenium Compounds* / chemistry
  • Selenium Compounds* / pharmacology

Substances

  • Antineoplastic Agents
  • Cytotoxins
  • Enzyme Inhibitors
  • Neoplasm Proteins
  • Organoselenium Compounds
  • Selenium Compounds
  • Glutathione Transferase