Abstract
The synthesis of new 4-amino substituted pyrazolo[3,4-d]pyrimidines along with their activity in cell-free enzymatic assays on Src and Abl tyrosine kinases is reported. Some compounds emerged as good dual inhibitors of the two enzymes, showed antiproliferative effects on two Bcr-Abl positive leukemia cell lines K-562 and KU-812, and induced apoptosis, as demonstrated by the PARP assay. Docking studies have been also performed to analyze the binding mode of compounds under study and to identify the structural determinants of their interaction with both Src and Abl.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology
-
CSK Tyrosine-Protein Kinase
-
Cell Proliferation / drug effects
-
Computer Simulation*
-
Drug Screening Assays, Antitumor
-
Fusion Proteins, bcr-abl / antagonists & inhibitors
-
Humans
-
Models, Chemical*
-
Molecular Structure
-
Protein Kinase Inhibitors / chemical synthesis*
-
Protein Kinase Inhibitors / chemistry
-
Protein Kinase Inhibitors / pharmacology*
-
Protein-Tyrosine Kinases / antagonists & inhibitors
-
Pyrazoles / chemistry*
-
Pyrimidines / chemical synthesis*
-
Pyrimidines / chemistry
-
Pyrimidines / pharmacology*
-
Recombinant Proteins / antagonists & inhibitors
-
Stereoisomerism
-
Structure-Activity Relationship
-
Tumor Cells, Cultured
-
src-Family Kinases
Substances
-
Antineoplastic Agents
-
Protein Kinase Inhibitors
-
Pyrazoles
-
Pyrimidines
-
Recombinant Proteins
-
Protein-Tyrosine Kinases
-
CSK Tyrosine-Protein Kinase
-
Fusion Proteins, bcr-abl
-
src-Family Kinases
-
CSK protein, human