Synthesis and investigation of dihydroxychalcones as calpain and cathepsin inhibitors

Bioorg Chem. 2013 Dec:51:24-30. doi: 10.1016/j.bioorg.2013.09.002. Epub 2013 Sep 16.

Abstract

In order to identify potential calpain and cathepsin inhibitors we prepared 12 dihydroxychalcone analogues and tested their ability to inhibit μ-calpain, m-calpain, cathepsins B and L. In the calpain inhibition test, compound 10 exhibited the most active inhibitory activity against m-calpain with an IC50 value of 25.25±0.901μM. With respect to inhibition of cathepsins B and L, compound 13 exhibited the most potent inhibitory activity on cathepsin L and moderate inhibitory activity on cathepsin B with IC50 values of 2.80±0.100 and 11.47±0.087μM, respectively. Our results suggest the possibility of developing dual calpain and cathepsin inhibitors by properly modulating structures and/or combining the essential aspects of the functional group effective for specific calpain and cathepsin inhibition.

Keywords: Calpain inhibitor; Cathepsin B; Dihydroxychalcone; L Inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calpain / antagonists & inhibitors*
  • Calpain / metabolism
  • Cathepsins / antagonists & inhibitors*
  • Cathepsins / metabolism
  • Chalcones / chemical synthesis*
  • Chalcones / chemistry
  • Chalcones / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Chalcones
  • Protease Inhibitors
  • Cathepsins
  • Calpain