Synthesis of bioactive and fluorescent pyridine-triazole-coumarin peptidomimetics through sequential click-multicomponent reactions

Bioorg Med Chem Lett. 2017 Feb 1;27(3):450-455. doi: 10.1016/j.bmcl.2016.12.044. Epub 2016 Dec 18.

Abstract

An easy synthetic protocol for the peptide randomization of 3,5-dicyano pyridine derivatives by linking the pyridine core with a coumarin chromophore spaced by a linker triazole via copper (I) catalyzed [3+2] azide-alkyne cycloaddition (CuAAC) is described. The new peptidomimetics thus obtained are extended rule of 5 (eRo5) molecules suitable for the development of therapeutic agents for undruggable targets. The structural and photophysical properties of the molecules are also promising for the development of potential bio imaging agents based on these molecules.

Keywords: 1,2,3-Triazole; Fluorescence; MCR-click; Peptidomimetics; eRo5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Azides / chemistry
  • Catalysis
  • Cell Survival / drug effects
  • Copper / chemistry
  • Coumarins / chemistry*
  • Cycloaddition Reaction
  • Humans
  • MCF-7 Cells
  • Microscopy, Fluorescence
  • Peptidomimetics*
  • Pyridines / chemistry*
  • Quantum Theory
  • Triazoles / chemistry*

Substances

  • Alkynes
  • Antineoplastic Agents
  • Azides
  • Coumarins
  • Peptidomimetics
  • Pyridines
  • Triazoles
  • Copper
  • coumarin
  • pyridine