Multi-Armed 1,2,3-Selenadiazole and 1,2,3-Thiadiazole Benzene Derivatives as Novel Glyoxalase-I Inhibitors

Molecules. 2019 Sep 4;24(18):3210. doi: 10.3390/molecules24183210.

Abstract

Glyoxalase-I (Glo-I) enzyme was established to be a valid target for anticancer drug design. It performs the essential detoxification step of harmful byproducts, especially methylglyoxal. A robust computer-aided drug design approach was used to design and validate a series of compounds with selenium or sulfur based heterorings. A series of in-house multi-armed 1,2,3-selenadiazole and 1,2,3-thiadiazole benzene derivatives were tested for their Glo-I inhibitory activity. Results showed that these compounds bind Glo-I active sites competitively with strong potential to inhibit this enzyme with IC50 values in micro-molar concentration. Docking poses revealed that these compounds interact with the zinc atom at the bottom of the active site, which plays an essential role in its viability.

Keywords: 1,2,3-Selenadiazole; 1,2,3-Thiadiazole; Glyoxalase-I; Inhibition; Zinc Binding Feature.

MeSH terms

  • Acetanilides / chemistry
  • Acetanilides / pharmacology*
  • Binding Sites
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydrogen Bonding
  • Lactoylglutathione Lyase / antagonists & inhibitors*
  • Lactoylglutathione Lyase / chemistry
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • 1,2,3-selenadiazole thioacetanilide
  • Acetanilides
  • Enzyme Inhibitors
  • Lactoylglutathione Lyase