Design, Synthesis, Anticancer Evaluation and <i>In Silico</i> Studies of Imidazole Pyrazine Compounds

The present study focused on design and synthesis novel imidazolopyrazine derivatives, investigate the effect of them on the proliferation and migration of several human cancer cell lines by CCK-8 method, and interactions with the JAKs by reverse molecular docking. It was found that most of the synthesized imidazolopyrazin derivatives exhibited excellent inhibitory effects towards three tested tutor cells in vitro. Among them, three compounds have IC₅₀ values much lower than Fluorouracil while show low toxicity to normal cells L-02. The migration ability assay have proved that A6 and A9 effectively inhibit the migration of tumor cells. Reverse molecular docking studies indicated that the potent targets of these derivatives are JAKs as they well docked into kinases with low energy. These finding suggest that imidazo[1,5-a]pyrazin derivatives may be lead compounds for developing potent JAK targeted anticancer candidates.