3,6-dibromocarbazole piperazine derivatives of 2-propanol as first inhibitors of cytochrome c release via Bax channel modulation

  • J Med Chem. 2003 Oct 9;46(21):4365-8. doi: 10.1021/jm034107j.
Agnes Bombrun  1 ,  Patrick Gerber ,  Giulio Casi ,  Olivier Terradillos ,  Bruno Antonsson ,  Serge Halazy
Affiliations
  • 1. Serono Pharmaceutical Research Institute, 14 Chemin des Aulx, 1228 Plan-les-Ouates, Geneva, Switzerland. [email protected]
PMID: 14521400 DOI: 10.1021/jm034107j
Abstract

There is compelling evidence that Bax channel activity stimulates cytochrome c release leading ultimately to cell death, which is a key event in ischemic injuries and neurodegenerative diseases. Here 3,6-dibromocarbazole piperazine derivatives of 2-propanol are described as the first small and potent modulators of the cytochrome c release triggered by Bid-induced Bax activation in a mitochondrial assay. Furthermore, a mechanism of action is proposed, and fluorescent derivatives allowing the localization of such inhibitors are reported.