Design, synthesis and biological evaluation of 3-aryl-rhodanine benzoic acids as anti-apoptotic protein Bcl-2 inhibitors

Bioorg Med Chem Lett. 2015 Nov 15;25(22):5265-9. doi: 10.1016/j.bmcl.2015.09.051. Epub 2015 Sep 25.

Abstract

A new class of 3-aryl-rhodanine benzoic acid derivatives were designed, synthesized, and evaluated for their inhibition activities against anti-apoptotic Bcl-2 proteins. The potent compounds 33 and 41 bound to Bcl-2 with submicromolar Ki values and had selectivities to Bcl-2/Mcl-1 over Bcl-xL. In addition, they exhibited obvious antiproliferative activities in three human tumor cell lines (MDA-MB-231, K562 and PC-3).

Keywords: Apoptosis; Bcl-2; Inhibitor; Rhodanine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Benzoates / chemical synthesis
  • Benzoates / pharmacology*
  • Cell Line, Tumor
  • Humans
  • Molecular Docking Simulation
  • Myeloid Cell Leukemia Sequence 1 Protein / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-bcl-2 / ultrastructure
  • Rhodanine / analogs & derivatives*
  • Rhodanine / chemical synthesis
  • Rhodanine / pharmacology
  • Sulfonamides / pharmacology
  • Thiazoles / pharmacology
  • bcl-X Protein / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • BCL2 protein, human
  • BCL2L1 protein, human
  • Benzoates
  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Sulfonamides
  • Thiazoles
  • WL 276
  • bcl-X Protein
  • Rhodanine