Tricyclic benzimidazoles as potent poly(ADP-ribose) polymerase-1 inhibitors

  • J Med Chem. 2003 Jan 16;46(2):210-3. doi: 10.1021/jm0255769.
Donald J Skalitzky  1 ,  Joseph T Marakovits ,  Karen A Maegley ,  Anne Ekker ,  Xiao-Hong Yu ,  Zdenek Hostomsky ,  Stephen E Webber ,  Brian W Eastman ,  Robert Almassy ,  Jianke Li ,  Nicola J Curtin ,  David R Newell ,  A Hilary Calvert ,  Roger J Griffin ,  Bernard T Golding
Affiliations
  • 1. Pfizer Global R&D, La Jolla/Agouron Pharmaceuticals, Inc., San Diego, California 92121, USA.
PMID: 12519059 DOI: 10.1021/jm0255769
Abstract

Novel tricyclic benzimidazole carboxamide poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been synthesized. Several compounds were found to be powerful chemopotentiators of temozolomide and topotecan in both A549 and LoVo cell lines. In vitro inhibition of PARP-1 was confirmed by direct measurement of NAD+ depletion and ADP-ribose polymer formation caused by chemically induced DNA damage.