Design, synthesis and preliminary bioactivity studies of 2-thioxo-4-thiazolidinone derivatives as Bcl-2 inhibitors

Bioorg Med Chem. 2015 May 1;23(9):1994-2003. doi: 10.1016/j.bmc.2015.03.024. Epub 2015 Mar 14.

Abstract

The B-cell lymphoma-2 (Bcl-2) protein is a promising target for cancer therapy. In the present study, a series of 2-thioxo-4-thiazolidinone derivatives were designed and synthesized as Bcl-2 inhibitors. Most of them possessed decent inhibitory activity for anti-apoptotic Bcl-2 proteins. Among them, compound 31 has similar growth inhibition towards K562 compared to (R)-Gossypol. In addition, it inhibits the myeloid cell leukemia sequence 1 (Mcl-1) protein with a Ki value of 74 nM.

Keywords: 2-Thioxo-4-thiazolidinone; Anti-tumor; Bcl-2; Inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • K562 Cells
  • Models, Molecular
  • Molecular Structure
  • Myeloid Cell Leukemia Sequence 1 Protein / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Thiazolidines / chemical synthesis
  • Thiazolidines / chemistry
  • Thiazolidines / pharmacology*

Substances

  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Thiazolidines