Synthesis and biological evaluation of novel synthetic chalcone derivatives as anti-tumor agents targeting Cat L and Cat K

Bioorg Med Chem. 2018 Jan 1;26(1):8-16. doi: 10.1016/j.bmc.2017.09.019. Epub 2017 Sep 18.

Abstract

A series of chalcone derivatives bearing benzamide or benzenesulfonamide moieties were synthesized and evaluated for their anti-tumor effect on HCT116, MCF7 and 143B cell lines in vitro. SAR analysis showed that compounds bearing a benzenesulfonamide group had greater potency than those bearing a benzamide group. It was also shown that compounds with a mono-methyl or mono-halogen group at the 3-position on the terminal phenyl ring were more effective than those with trifluoromethyl or methoxy groups. Compound 8e exhibited the most potent anti-tumor activities against HCT116, MCF7 and 143B cell lines, with IC50 values of 0.597, 0.886 and 0.791μM, respectively. Molecular docking studies and enzymatic assays demonstrated that the anti-tumor activity of compound 8e might be regulated by Cat L and Cat K.

Keywords: Anti-tumor activity; Cat K; Cat L; Chalcone.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cathepsin K / antagonists & inhibitors*
  • Cathepsin L / antagonists & inhibitors*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chalcone / chemical synthesis
  • Chalcone / chemistry
  • Chalcone / pharmacology*
  • Cysteine Proteinase Inhibitors / chemical synthesis
  • Cysteine Proteinase Inhibitors / chemistry
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Cysteine Proteinase Inhibitors
  • Chalcone
  • CTSL protein, human
  • Cathepsin L
  • CTSK protein, human
  • Cathepsin K