Design, synthesis, and anticancer evaluation of N⁶ -hydrazone purine derivatives with potential...

In our research on novel anticancer agents, a series of N⁶ -hydrazone purine derivatives were designed and synthesized by analysis of a pharmacophore model for ATP-competitive inhibitors. The activities screening results showed that N⁶ -hydrazone purine derivatives 21 and 26 not only showed potential antiproliferative activity against the A549 and MCF-7 cell lines comparable to Vandetanib as a positive control but also had moderate antiplatelet aggregation activity. In order to investigate the possible targets, a molecular docking study was carried out on the fourteen kinases associated with anticancer and antiplatelet aggregation activities. The results indicated that compounds 21 and 26 had the potential activity to target VEGFR-2, PI3Kα, EGFR, and HER2 kinases. The inhibition of the kinases assay showed that compound 26 could target VEGFR-2, PI3Kα, and EGFR (IC₅₀  = 0.822, 3.040 and 6.625 μM). All results indicated that compound 26 will be an encouraging framework as potential new multi-target anticancer agent with potential antiplatelet aggregation activity.