Design, synthesis and preliminary bioactivity studies of imidazolidine-2,4-dione derivatives as Bcl-2 inhibitors

Bioorg Med Chem. 2015 Dec 1;23(23):7359-65. doi: 10.1016/j.bmc.2015.10.023. Epub 2015 Oct 23.

Abstract

Anti-apoptotic B-cell lymphoma-2 (Bcl-2) proteins are promising targets for cancer therapy. In the present study, a series of imidazolidine-2,4-dione derivatives were designed and synthesized to test their inhibitory activities against anti-apoptotic Bcl-2 proteins. Among them, compound 8k had better growth inhibitory effects on K562 and PC-3 cell lines compared to lead compound WL-276.

Keywords: Antitumor; Bcl-2; Imidazolidine-2,4-dione; Inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Humans
  • Hydantoins / chemical synthesis
  • Hydantoins / pharmacology*
  • Molecular Docking Simulation
  • Myeloid Cell Leukemia Sequence 1 Protein / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / pharmacology*
  • Thiazoles / pharmacology
  • bcl-X Protein / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • Hydantoins
  • Myeloid Cell Leukemia Sequence 1 Protein
  • N-(4-chloro-3-nitrophenylsulfonyl)-2-(4-((3'-methylbiphenyl-4-yl)methyl)-2,5-dioxoimidazolidin-1-yl)-3-phenylpropanamide
  • Sulfonamides
  • Thiazoles
  • WL 276
  • bcl-X Protein