Pyrogallol-based molecules as potent inhibitors of the antiapoptotic Bcl-2 proteins

J Med Chem. 2007 Apr 19;50(8):1723-6. doi: 10.1021/jm061400l. Epub 2007 Mar 23.

Abstract

We report herein a new class of small-molecule inhibitors of antiapoptotic Bcl-2 proteins. The most potent compound, 7, binds to Bcl-2, Bcl-xL, and Mcl-1 proteins with Ki of 110, 638, and 150 nM, respectively. Compound 7 is highly effective in induction of cell death in breast cancer cells with high levels of Bcl-2, Bcl-xL, and Mcl-1 proteins and represents a promising lead compound for the design of new anticancer drugs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Apoptosis*
  • Binding, Competitive
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Humans
  • Models, Molecular
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Pyrogallol / analogs & derivatives*
  • Pyrogallol / chemical synthesis*
  • Pyrogallol / pharmacology
  • Radioligand Assay
  • Structure-Activity Relationship
  • bcl-X Protein / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • Pyrogallol