Design, synthesis, biological evaluation and molecular docking studies of new chalcone derivatives containing diaryl ether moiety as potential anticancer agents and tubulin polymerization inhibitors

Bioorg Chem. 2020 Jan:95:103565. doi: 10.1016/j.bioorg.2019.103565. Epub 2019 Dec 31.

Abstract

A novel series of chalcone derivatives containing diaryl ether moiety (5a-5p) were designed, synthesized and evaluated their anti-tubulin polymerization activities and anticancer activities. Among them, compound 5b with 4-methoxy substitution on right aromatic ring was found to be most active on MCF-7, HepG2 and HCT116 cancer cell lines, with IC50 values of 3.44 ± 0.19, 4.64 ± 0.23, and 6.31 ± 0.27 μM, respectively. In vitro tubulin polymerization assay showed that 5b could effectively inhibit tubulin polymerization. Further mechanism studies revealed that 5b could induce G2/M phase arrest and cell apoptosis. Molecular docking studies revealed that 5b interact and bind at the colchicine binding site of the tubulin.

Keywords: Anticancer agents; Chalcone; Diaryl ether; Tubulin polymerization inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chalcones / chemistry
  • Chalcones / pharmacology*
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Humans
  • Molecular Docking Simulation
  • Polymerization / drug effects*
  • Structure-Activity Relationship
  • Tubulin / chemistry*
  • Tubulin Modulators / chemical synthesis
  • Tubulin Modulators / chemistry*
  • Tubulin Modulators / pharmacology*

Substances

  • Antineoplastic Agents
  • Chalcones
  • Tubulin
  • Tubulin Modulators