Synthesis and biological evaluation of novel 2-heteroarylimino-1,3-thiazolidin-4-ones as potential anti-tumor agents

Eur J Med Chem. 2015 Apr 13:94:102-12. doi: 10.1016/j.ejmech.2015.02.053. Epub 2015 Feb 28.

Abstract

A series of 35 heteroarylimino-1,3-thiazolidinones with three sites of functionalization were synthesized and their antiproliferative properties were studied. The in vitro screening by MTT assay was performed against five cancer cell lines (human colon cancer cell lines HT29, HCT116 and SW620 and breast cancer cell lines MCF7 and MDA-MB-231). It was observed that N3-substituted thiazolidinones had moderate activities whereas 5-benzylidene thiazolidinones showed promising activities. To investigate the mechanism of action, detailed biological studies of six selected compounds (those presenting the lower mitotic index) were carried out on the human colon cancer HT29 cell line. Cell cycle assay revealed that those compounds induced cell accumulation in G2/M and in subG0/G1 phases of cell cycle. Moreover, dissipation of mitochondria membrane potential was observed as well as redox changes in treated cells.

Keywords: Antiproliferative activity; Colon cancer; Thiazole; Thiazolidinone; Thiophene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Autophagy / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Chemistry Techniques, Synthetic
  • Drug Screening Assays, Antitumor
  • Humans
  • Inhibitory Concentration 50
  • Membrane Potential, Mitochondrial / drug effects
  • Oxidation-Reduction
  • Structure-Activity Relationship
  • Thiazolidines / chemistry

Substances

  • Antineoplastic Agents
  • Thiazolidines