Synthesis and biological evaluation of novel N-methyl-picolinamide-4-thiol derivatives as potential antitumor agents

Molecules. 2012 May 25;17(6):6317-30. doi: 10.3390/molecules17066317.

Abstract

A novel series of N-methylpicolinamide-4-thiol derivatives were synthesized and evaluated on human cancer cell lines. Among them, compound 6p displayed potent and broad-spectrum anti-proliferative activities in vitro on some human cancer cell lines, even better than sorafenib. The advanced kinase inhibitory assays showed that compound 6p could selectively inhibit Aurora-B kinase. The biological results were rationalized by the molecular docking study, which indicated the stable interactions of 6p with the Aurora-B kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Aurora Kinase B
  • Aurora Kinases
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Molecular Dynamics Simulation
  • Picolinic Acids / chemical synthesis*
  • Picolinic Acids / pharmacology*
  • Protein Binding
  • Protein Conformation
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / chemistry
  • Sulfhydryl Compounds / chemical synthesis*
  • Sulfhydryl Compounds / pharmacology*

Substances

  • Antineoplastic Agents
  • N-methyl-picolinamide-4-thiol
  • Picolinic Acids
  • Protein Kinase Inhibitors
  • Sulfhydryl Compounds
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases