The effect of RO3201195 and a pyrazolyl ketone P38 MAPK inhibitor library on the proliferation of Werner syndrome cells

Org Biomol Chem. 2016 Jan 21;14(3):947-56. doi: 10.1039/c5ob02229k. Epub 2015 Nov 27.

Abstract

Microwave-assisted synthesis of the pyrazolyl ketone p38 MAPK inhibitor RO3201195 in 7 steps and 15% overall yield, and the comparison of its effect upon the proliferation of Werner Syndrome cells with a library of pyrazolyl ketones, strengthens the evidence that p38 MAPK inhibition plays a critical role in modulating premature cellular senescence in this progeroid syndrome and the reversal of accelerated ageing observed in vitro on treatment with SB203580.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Fibroblasts / drug effects
  • Fibroblasts / pathology
  • Humans
  • Ketones / chemical synthesis
  • Ketones / chemistry
  • Ketones / pharmacology*
  • Microwaves
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship
  • Werner Syndrome / drug therapy
  • Werner Syndrome / metabolism
  • Werner Syndrome / pathology*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • 5-amino-1-(4-fluorophenyl)-4-(3-(2,3-dihydroxypropoxy)benzoyl)pyrazole
  • Ketones
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Small Molecule Libraries
  • p38 Mitogen-Activated Protein Kinases