New inhibitors of protein kinase CK2, analogues of benzimidazole and benzotriazole

Mol Cell Biochem. 2008 Sep;316(1-2):87-9. doi: 10.1007/s11010-008-9827-0. Epub 2008 Jun 12.

Abstract

Derivatives of 4,5,6,7-tetrabromobenzotriazole (TBBt) and 4,5,6,7-tetrabromobenzimidazole (TBBi) with IC50 in the low micromolar range and with high selectivity belong to the most promising inhibitors of protein kinase CK2 (casein kinase 2). Treatment of various cell lines with TBBt, TBBi or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) affected cell viability with simultaneous induction of apoptosis. The inhibitory activity of newly synthesized hydroxyalkyl derivatives of TBBi and TBBt depends on the length of the alkyl chain. The hydroxypropyl substituted derivatives show higher or similar inhibitory activity than the parent compounds when tested with human protein kinase CK2. To test the distribution of this class of compounds in mammals, [14C] TBBi was synthesized.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzimidazoles / chemistry*
  • Casein Kinase II / antagonists & inhibitors*
  • Humans
  • Protein Kinase Inhibitors / analysis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Triazoles / analysis
  • Triazoles / chemistry*
  • Triazoles / pharmacology

Substances

  • 4,5,6,7-tetrabromobenzotriazole
  • Benzimidazoles
  • Protein Kinase Inhibitors
  • Triazoles
  • benzotriazole
  • benzimidazole
  • Casein Kinase II