Structure-activity relationship study of 4-(thiazol-5-yl)benzoic acid derivatives as potent protein kinase CK2 inhibitors

Bioorg Med Chem. 2016 Mar 1;24(5):1136-41. doi: 10.1016/j.bmc.2016.01.043. Epub 2016 Jan 22.

Abstract

Two classes of modified analogs of 4-(thiazol-5-yl)benzoic acid-type CK2 inhibitors were designed. The azabenzene analogs, pyridine- and pyridazine-carboxylic acid derivatives, showed potent protein kinase CK2 inhibitory activities [IC50 (CK2α)=0.014-0.017μM; IC50 (CK2α')=0.0046-0.010μM]. Introduction of a 2-halo- or 2-methoxy-benzyloxy group at the 3-position of the benzoic acid moiety maintained the potent CK2 inhibitory activities [IC50 (CK2α)=0.014-0.016μM; IC50 (CK2α')=0.0088-0.014μM] and led to antiproliferative activities [CC50 (A549)=1.5-3.3μM] three to six times higher than those of the parent compound.

Keywords: Kinase inhibitor; Protein kinase CK2; Rational design; Structure–activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoic Acid / chemistry*
  • Benzoic Acid / pharmacology*
  • Casein Kinase II / antagonists & inhibitors
  • Casein Kinase II / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Models, Molecular
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Thiazoles / chemistry
  • Thiazoles / pharmacology

Substances

  • Protein Kinase Inhibitors
  • Thiazoles
  • Benzoic Acid
  • CSNK2A1 protein, human
  • Casein Kinase II