Synthesis, Pim kinase inhibitory potencies and in vitro antiproliferative activities of diversely substituted pyrrolo[2,3-a]carbazoles

Bioorg Med Chem. 2010 Sep 15;18(18):6865-73. doi: 10.1016/j.bmc.2010.07.036. Epub 2010 Aug 19.

Abstract

The synthesis of new pyrrolo[2,3-a]carbazole derivatives diversely substituted at the C-6 to C-9 positions is described. These compounds were tested for their kinase inhibitory potencies toward three kinases (Pim-1, Pim-2, Pim-3) as well as for their in vitro antiproliferative activities toward a human fibroblast primary culture and three human solid cancer cell lines (PC3, DU145, and PA 1). Moreover, molecular docking studies were performed to explain the enhanced inhibitory activity of the most active compound 3d.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity
  • Binding Sites
  • Carbazoles / chemical synthesis
  • Carbazoles / chemistry*
  • Carbazoles / toxicity
  • Cell Line
  • Computer Simulation
  • Humans
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / toxicity
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-pim-1 / metabolism

Substances

  • 6-bromo-1,10-dihydropyrrolo(2,3-a)carbazole-3-carbaldehyde
  • Antineoplastic Agents
  • Carbazoles
  • PIM2 protein, human
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • PIM3 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-pim-1