Inhibitors of glucosamine-6-phosphate synthase as potential antimicrobials or antidiabetics - synthesis and properties

J Enzyme Inhib Med Chem. 2022 Dec;37(1):1928-1956. doi: 10.1080/14756366.2022.2096018.

Abstract

Glucosamine-6-phosphate synthase (GlcN-6-P synthase) is known as a promising target for antimicrobial agents and antidiabetics. Several compounds of natural or synthetic origin have been identified as inhibitors of this enzyme. This set comprises highly selective l-glutamine, amino sugar phosphate or transition state intermediate cis-enolamine analogues. Relatively low antimicrobial activity of these inhibitors, poorly penetrating microbial cell membranes, has been improved using the pro-drug approach. On the other hand, a number of heterocyclic and polycyclic compounds demonstrating antimicrobial activity have been presented as putative inhibitors of the enzyme, based on the results of molecular docking to GlcN-6-P synthase matrix. The most active compounds of this group could be considered promising leads for development of novel antimicrobial drugs or antidiabetics, provided their selective toxicity is confirmed.

Keywords: Glucosamine-6-phosphate synthase; antibacterial agents; antifungal agents; diabetes; drug synthesis.

MeSH terms

  • Anti-Infective Agents*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)* / metabolism
  • Hypoglycemic Agents
  • Molecular Docking Simulation

Substances

  • Anti-Infective Agents
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)