Synthesis and evaluation of quinazolinone derivatives as inhibitors of NF-kappaB, AP-1 mediated transcription and eIF-4E mediated translational activation: inhibitors of multi-pathways involve in cancer

Eur J Med Chem. 2010 Sep;45(9):3558-63. doi: 10.1016/j.ejmech.2010.04.038. Epub 2010 May 7.

Abstract

In our effort to discover and develop small molecule multi-pathway inhibitors which may be useful as tools for treating cancerous conditions, we have synthesized a small library of 2-thiazole-5-yl-3H-quinazolin-4-one derivatives. Synthesized compounds were evaluated as inhibitors of NF-kappaB and AP-1 mediated transcriptional and eIF-4E mediated translational activation as these transcription and translation factors are known to play a pivotal role in initiation and progression of cancer. The results from the study suggest the utility of the 2-thiazole-5-yl-3H-quinazolin-4-one scaffold as a promising scaffold for the design of novel multi-pathway inhibitors, which can be explored as anti-cancer agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Base Sequence
  • Cell Line
  • Eukaryotic Initiation Factor-4E / metabolism*
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / chemistry
  • NF-kappa B / metabolism*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Protein Biosynthesis / drug effects*
  • Protein Conformation
  • Quinazolinones / chemical synthesis
  • Quinazolinones / chemistry
  • Quinazolinones / pharmacology*
  • Transcription Factor AP-1 / antagonists & inhibitors
  • Transcription Factor AP-1 / metabolism*
  • Transcription, Genetic / drug effects*

Substances

  • Antineoplastic Agents
  • Eukaryotic Initiation Factor-4E
  • NF-kappa B
  • Quinazolinones
  • Transcription Factor AP-1