1,2,3-Triazole-nimesulide hybrid: Their design, synthesis and evaluation as potential anticancer agents

Bioorg Med Chem Lett. 2017 Feb 1;27(3):518-523. doi: 10.1016/j.bmcl.2016.12.030. Epub 2016 Dec 10.

Abstract

A new hybrid template has been designed by integrating the structural features of nimesulide and the 1,2,3-triazole moiety in a single molecular entity at the same time eliminating the problematic nitro group of nimesulide. The template has been used for the generation of a library of molecules as potential anticancer agents. A mild and greener CuAAC approach has been used to synthesize these compounds via the reaction of 4-azido derivative of nimesulide and terminal alkynes in water. Three of these compounds showed promising growth inhibition (IC50 ∼6-10μM) of A549, HepG2, HeLa and DU145 cancer cell lines but no significant effects on HEK293 cell line. They also inhibited PDE4B in vitro (60-70% at 10μM) that was supported by the docking studies (PLP score 87-94) in silico.

Keywords: 1,2,3-Triazole; Alkyne; Anticancer activity; Azide; Nimesulide.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • HEK293 Cells
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Phosphodiesterase 4 Inhibitors / chemical synthesis
  • Phosphodiesterase 4 Inhibitors / chemistry
  • Phosphodiesterase 4 Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Antineoplastic Agents
  • Phosphodiesterase 4 Inhibitors
  • Triazoles
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • PDE4B protein, human