Synthesis, In Vitro and In Silico Anticancer Activity of New 4-Methylbenzamide Derivatives Containing 2,6-Substituted Purines as Potential Protein Kinases Inhibitors.

A novel class of potential protein kinase inhibitors - was synthesized in high yields using various substituted purines. The most promising compounds, and exhibited inhibitory activity against seven cancer cell lines. The IC values for compounds and were 2.27 and 2.53 μM for K562 cells, 1.42 and 1.52 μM for HL-60 cells, and 4.56 and 24.77 μM for OKP-GS cells, respectively. In addition, compounds and dose-dependently induced the apoptosis and cell cycle arrest at G2/M phase, preventing the cell division of OKP-GS cells. Compounds , and showed 36-45% inhibitory activity against PDGFRα and PDGFRβ at the concentration of 1 μM. Molecular modeling experiments showed that obtained compounds could bind to PDGFRα as either type 1 (compound , ATP-competitive) or type 2 (compound , allosteric) inhibitors, depending on the substituent in the amide part of the molecule.