Insight on [1,3]thiazolo[4,5-e]isoindoles as tubulin polymerization inhibitors

Eur J Med Chem. 2021 Feb 15:212:113122. doi: 10.1016/j.ejmech.2020.113122. Epub 2020 Dec 24.

Abstract

A series of [1,3]thiazolo[4,5-e]isoindoles has been synthesized through a versatile and high yielding multistep sequence. Evaluation of the antiproliferative activity of the new compounds on the full NCI human tumor cell line panel highlighted several compounds that are able to inhibit tumor cell proliferation at micromolar-submicromolar concentrations. The most active derivative 11g was found to cause cell cycle arrest at the G2/M phase and induce apoptosis in HeLa cells, following the mitochondrial pathway, making it a lead compound for the discovery of new antimitotic drugs.

Keywords: 1,3]thiazolo[4,5-e]isoindoles; Apoptosis; Cell cycle arrest; Tubulin polymerization inhibitors.

MeSH terms

  • Apoptosis / drug effects
  • Dose-Response Relationship, Drug
  • HeLa Cells
  • Humans
  • Isoindoles / chemical synthesis
  • Isoindoles / chemistry
  • Isoindoles / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Polymerization / drug effects
  • Structure-Activity Relationship
  • Tubulin / metabolism*
  • Tubulin Modulators / chemical synthesis
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology*

Substances

  • Isoindoles
  • Tubulin
  • Tubulin Modulators