Synthesis and Biological Evaluation of Imadazo[1,2-]pyrazines as Anticancer and Antiviral Agents through Inhibition of CDK9 and Human Coronavirus.

In this work, novel imadazo[1,2-]pyrazine derivatives were synthesized and evaluated as CDK9 inhibitors. The results of CDK9 assay showed that the derivatives with pyridin-4-yl in position 2 and benzyl in position 3 of imadazo[1,2-]pyrazine displayed the most potent CDK9 inhibitory activity with IC of 0.16 µM. The anti-proliferative effect of the new compounds was examined against breast cancer (MCF7), colorectal cancer (HCT116), and chronic myelogenous leukaemia (K652) cell lines. The data of MTT assay showed that the cytotoxic effect of the inhibitors is correlated to their inhibitory activity against CDK9. Compound exhibited the most potent cytotoxicity effect with average ICs of three cell lines of 6.66 µM. The drug likeness properties of were predicated in silico and demonstrated that have reasonable physiochemical and pharmacokinetic properties. Selected derivatives were assessed in antiviral assay against human coronavirus 229E. The results of this assay showed that the derivative with pyridin-4-yl in position 2 and cyclohexyl in position 3 of imadazo[1,2-]pyrazine exhibited the most potent anti-coronaviral activity with IC of 56.96 µM and selectivity index of 7.14. The target predication result revealed that showed high affinity to protease enzyme. Docking studies of with COVID-19 main protease was conducted and showed good binding affinity, which confirmed the in vitro assay data.