Synthetic chalcone derivatives as inhibitors of cathepsins K and B, and their cytotoxic evaluation

Chem Biodivers. 2013 Nov;10(11):1999-2006. doi: 10.1002/cbdv.201200344.

Abstract

A series of chalcone derivatives, 1-15, were prepared by Claisen-Schmidt condensation and evaluated for their cytotoxicities on tumor cell lines and also against proteolytic enzymes such as cathepsins B and K. Of the compounds synthesized, (E)-3-(3,4-dimethoxyphenyl)-1-phenylprop-2-en-1-one (12), (E)-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one (13), (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (14), and (E)-3-(4-nitrophenyl)-1-phenylprop-2-en-1-one (15) showed significant cytotoxicities. The most effective compound was 15, which showed high cytotoxic activity with an IC50 value lower than 1 μg/ml, and no selectivity on the tumor cells evaluated. Substituents at C(4) of ring B were found to be essential for cytotoxicity. In addition, it was also demonstrated that some of these chalcones are moderate inhibitors of cathepsin K and have no activity against cathepsin B.

Keywords: Cathepsins; Chalcones; Cytotoxic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cathepsin B / antagonists & inhibitors*
  • Cathepsin B / metabolism
  • Cathepsin K / antagonists & inhibitors*
  • Cathepsin K / metabolism
  • Cell Line, Tumor
  • Chalcone / analogs & derivatives*
  • Chalcone / pharmacology*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / enzymology

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Chalcone
  • Cathepsin B
  • Cathepsin K