Synthesis, biological evaluation and molecular docking studies of bis-chalcone derivatives as xanthine oxidase inhibitors and anticancer agents

Bioorg Chem. 2019 Oct:91:103149. doi: 10.1016/j.bioorg.2019.103149. Epub 2019 Jul 30.

Abstract

In this study, a series of B-ring fluoro substituted bis-chalcone derivatives were synthesized by Claisen-Schmidt condensation reactions and evaluated for their ability to inhibit xanthine oxidase (XO) and growth inhibitory activity against MCF-7 and Caco-2 human cancer cell lines, in vitro. According to the results obtained, the bis-chalcone with fluoro group at the 2 (4b) or 2,5-position (4g) of B-ring were found to be potent inhibitors of the enzyme with IC50 values in the low micromolar range. The effects of these compounds were about 7 fold higher than allopurinol. The binding modes of the bis-chalcone derivatives in the active site of xanthine oxidase were explained using molecular docking calculations. Also, compound 4g and 4h showed in vitro growth inhibitory activity against a panel of two human cancer cell lines 1.9 and 6.8 μM of IC50 values, respectively.

Keywords: Bis-chalcone; Claisen-Schmidt condensation; Cytotoxicity; Inhibition; Synthesis.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Catalytic Domain
  • Cell Proliferation
  • Cell Survival
  • Chalcone / chemistry*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • Xanthine Oxidase / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Chalcone
  • Xanthine Oxidase