Abstract
The synthesis and CDK inhibitory properties of a series of indolo[6,7-a]pyrrolo[3,4-c]carbazoles is reported. In addition to their potent CDK activity, the compounds display antiproliferative activity against two human cancer cell lines. These inhibitors also effect strong G1 arrest in these cell lines and inhibit Rb phosphorylation at Ser780 consistent with inhibition of cyclin D1/CDK4.
MeSH terms
-
Antineoplastic Agents / chemical synthesis*
-
Antineoplastic Agents / pharmacology*
-
Calcium-Calmodulin-Dependent Protein Kinase Type 2
-
Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
-
Carbazoles / chemical synthesis*
-
Carbazoles / pharmacology*
-
Cell Cycle / drug effects
-
Cell Division / drug effects
-
Cell Line, Tumor
-
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
-
Cyclin D1 / antagonists & inhibitors*
-
Cyclin-Dependent Kinase 4
-
Cyclin-Dependent Kinases / antagonists & inhibitors*
-
Drug Screening Assays, Antitumor
-
Enzyme Inhibitors / chemical synthesis
-
Enzyme Inhibitors / pharmacology
-
Humans
-
Phosphorylation
-
Proto-Oncogene Proteins*
-
Rubidium / metabolism
-
Structure-Activity Relationship
Substances
-
Antineoplastic Agents
-
Carbazoles
-
Enzyme Inhibitors
-
Proto-Oncogene Proteins
-
Cyclin D1
-
Cyclic AMP-Dependent Protein Kinases
-
Calcium-Calmodulin-Dependent Protein Kinase Type 2
-
Calcium-Calmodulin-Dependent Protein Kinases
-
CDK4 protein, human
-
Cyclin-Dependent Kinase 4
-
Cyclin-Dependent Kinases
-
Rubidium