Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety

Molecules. 2021 May 20;26(10):3041. doi: 10.3390/molecules26103041.

Abstract

Two series of olmutinib derivatives containing an acrylamide moiety were designed and synthesized, and their IC50 values against cancer cell lines (A549, H1975, NCI-H460, LO2, and MCF-7) were evaluated. Most of the compounds exhibited moderate cytotoxic activity against the five cancer cell lines. The most promising compound, H10, showed not only excellent activity against EGFR kinase but also positive biological activity against PI3K kinase. The structure-activity relationship (SAR) suggested that the introduction of dimethylamine scaffolds with smaller spatial structures was more favorable for antitumor activity. Additionally, the substitution of different acrylamide side chains had different effects on the activity of compounds. Generally, compounds H7 and H10 were confirmed as promising antitumor agents.

Keywords: EGFR; acrylamide; inhibitor; olmutinib derivatives.

MeSH terms

  • Acrylamide / chemistry*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Drug Design
  • Drug Screening Assays, Antitumor
  • ErbB Receptors / antagonists & inhibitors
  • Humans
  • Molecular Docking Simulation
  • Phosphatidylinositol 3-Kinases / drug effects
  • Piperazines / chemical synthesis
  • Piperazines / chemistry*
  • Piperazines / pharmacology*
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Acrylamide
  • olmutinib
  • ErbB Receptors