Abstract
We have previously demonstrated that pyrrolo[2,3-a]carbazole-3-carbaldehydes are potent Pim kinase inhibitors with in vitro antiproliferative activities. In the present study, we report the synthesis of new pyrrolocarbazoles substituted at the N-10 position. When their ability to inhibit Pim kinase activities were evaluated in in vitro assays, we observed that this nitrogen atom can be substituted without loss of Pim-1 and Pim-3 inhibitory potencies. Moreover, when we added a fluorescent dansyl group (compound 13), we were able to show that 13 penetrates the plasma membrane and enters the cytoplasm.
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Alkynes / chemistry*
-
Azides / chemistry*
-
Carbazoles / chemical synthesis*
-
Carbazoles / pharmacology
-
Catalysis
-
Cell Membrane / metabolism
-
Copper / pharmacology*
-
Cytoplasm / metabolism
-
Humans
-
Male
-
Molecular Structure
-
Prostatic Neoplasms / drug therapy*
-
Protein Kinase Inhibitors / chemical synthesis*
-
Protein Kinase Inhibitors / pharmacology
-
Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
-
Proto-Oncogene Proteins c-pim-1 / metabolism
-
Structure-Activity Relationship
-
Subcellular Fractions
-
Tumor Cells, Cultured
Substances
-
Alkynes
-
Azides
-
Carbazoles
-
Protein Kinase Inhibitors
-
Copper
-
Proto-Oncogene Proteins c-pim-1