查看文章

Calcium/calmodulin‐dependent protein kinase IV (CAMKIV) is a multifunctional Ser/Thr kinase, associated with cerebral hypoxia, cancer, and neurodegenerative diseases. Here, we report design, synthesis, and biological evaluation of seven pyrimidine‐substituted novel inhibitors of CAMKIV. We successfully synthesized and extensively characterized (ESI‐MS, ¹H NMR, and ¹³C NMR studies) seven compounds that are showing appreciable binding affinity to the CAMKIV. Molecular docking and fluorescence binding studies revealed that compound 1 is showing very high binding free energy (ΔG = −11.52 kcal/mol) and binding affinity (K = 9.2 × 10¹⁰ m⁻¹) to the CAMKIV. We further performed MTT assay to check the cytotoxicity and anticancer activity of these compounds. An appreciable IC₅₀ (39 μm) value of compound 1 was observed on human hepatoma cell line and nontoxic till the 400 μm on human …