Abstract
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 and biological activities (Pim kinase inhibition and in vitro antiproliferative potency) of new 4-substituted pyrrolo[2,3-a]carbazoles. The results demonstrated that the Pim kinase inhibitory potency (especially Pim-3) can be conserved for pyrrolo[2,3-a]carbazoles bearing a methoxycarbonyl group at the 4-position without a formyl at the 3-position. Moreover, compound 27 that was found to be active against Pim-1 and Pim-3 kinases showed antiproliferative activities in the micromolar range.
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology*
-
Carbazoles / chemical synthesis
-
Carbazoles / chemistry
-
Carbazoles / pharmacology*
-
Cell Proliferation / drug effects
-
Cell Survival / drug effects
-
Dose-Response Relationship, Drug
-
Drug Screening Assays, Antitumor
-
Humans
-
Models, Molecular
-
Molecular Structure
-
Protein Kinase Inhibitors / chemical synthesis
-
Protein Kinase Inhibitors / chemistry
-
Protein Kinase Inhibitors / pharmacology*
-
Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
-
Proto-Oncogene Proteins c-pim-1 / metabolism
-
Pyrroles / chemical synthesis
-
Pyrroles / chemistry
-
Pyrroles / pharmacology*
-
Structure-Activity Relationship
-
Tumor Cells, Cultured
Substances
-
Antineoplastic Agents
-
Carbazoles
-
Protein Kinase Inhibitors
-
Pyrroles
-
Proto-Oncogene Proteins c-pim-1
-
proto-oncogene proteins pim