Synthesis, biological evaluation and docking studies of 4-amino substituted 1H-pyrazolo[3,4-d]pyrimidines

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.

Graphical abstractA number of 4-amino substituted pyrazolo[3,4-d]pyrimidines have been synthesized and tested in cell-free enzymatic assays on Src and Abl tyrosine kinases. Some molecules emerged as good dual inhibitors and showed antiproliferative effects on leukemia cell lines, together with proapoptotic activity.Figure optionsDownload full-size imageDownload as PowerPoint slide