Design, Modeling and Synthesis of 1,2,3-Triazole-Linked Nucleoside-Amino Acid Conjugates as Potential Antibacterial Agents

Molecules. 2017 Oct 10;22(10):1682. doi: 10.3390/molecules22101682.

Abstract

Copper-catalyzed azide-alkyne cycloadditions (CuAAC or click chemistry) are convenient methods to easily couple various pharmacophores or bioactive molecules. A new series of 1,2,3-triazole-linked nucleoside-amino acid conjugates have been designed and synthesized in 57-76% yields using CuAAC. The azido group was introduced on the 5'-position of uridine or the acyclic analogue using the tosyl-azide exchange method and alkylated serine or proparylglycine was the alkyne. Modeling studies of the conjugates in the active site of LpxC indicate they have promise as antibacterial agents.

Keywords: 1,2,3-triazole; CuAAC; LpxC; antibacterial; click chemistry; nucleoside.

MeSH terms

  • Alkynes / chemistry
  • Amino Acids / chemistry*
  • Anti-Bacterial Agents / chemistry*
  • Azides / chemistry
  • Catalysis
  • Click Chemistry
  • Copper / chemistry
  • Cycloaddition Reaction
  • Models, Chemical
  • Molecular Structure
  • Nucleosides / chemistry*
  • Triazoles / chemistry*

Substances

  • Alkynes
  • Amino Acids
  • Anti-Bacterial Agents
  • Azides
  • Nucleosides
  • Triazoles
  • Copper