Novel imidazo[2,1-b]thiazole-based anticancer agents as potential focal adhesion kinase inhibitors: Synthesis, in silico and in vitro evaluation

Chem Biol Drug Des. 2021 Aug;98(2):270-282. doi: 10.1111/cbdd.13896. Epub 2021 Jun 12.

Abstract

The purpose of this study was to synthesize imidazo[2,1-b]thiazole derivatives, characterize them with spectroscopical techniques and investigate for cytotoxic and apoptotic effects on glioma C6 cancer cell line. The in vitro anticancer activities were also investigated against focal adhesion kinase. Most of the compounds, particularly the derivatives carrying 3-oxo-1-tiya-4-azaspiro[4.5]decane moiety, exhibited higher or comparable activities in comparison with the reference drug, cisplatin. Compounds with methyl, propyl, phenyl moieties at the eighth and second position of the spirothiazolidinone ring showed high FAK inhibitory activities. In addition, molecular docking studies shed light on the binding modes of the synthesized compounds. The critical interactions with amino acid residues located in the active site were revealed. The results obtained from both biological assay data and computational results might provide insight into developing new inhibitors against focal adhesion kinase.

Keywords: Imidazo[2,1-b]thiazole; focal adhesion kinase; molecular docking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Binding Sites
  • Catalytic Domain
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Humans
  • Imidazoles / chemistry*
  • Imidazoles / metabolism
  • Imidazoles / pharmacology
  • Molecular Docking Simulation
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Static Electricity
  • Structure-Activity Relationship
  • Thiazoles / chemistry*
  • Thiazoles / metabolism
  • Thiazoles / pharmacology

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Protein Kinase Inhibitors
  • Thiazoles
  • imidazo(2,1-b)thiazole
  • Focal Adhesion Protein-Tyrosine Kinases

Grants and funding