NOVEL HETEROCYCLIC COMPOUNDS AS KINASE INHIBITORS WITH ANTICANCER ACTIVITY IN MEDULLOBLASTOMA

Abstract AIMS Medulloblastoma is the most common malignant brain tumor of childhood. Protein kinases are often overexpressed and constitute targets for the development of novel molecularly-targeted therapies in brain tumors. Here, we report the synthesis of new derivatives with kinase inhibitory activity and their anticancer activity in an early screening in medulloblastoma cells. METHOD The synthesis route was performed through six steps using a proper amino acid as starting material. The inhibitory activity of the final derivatives on the protein kinase was measured by fluorescence. Cultured DAOY medulloblastoma cells were used to examine anticancer activity. RESULTS The compounds display potent inhibitory activity on viability of DAOY medulloblastoma cells. The more promising derivative shows IC50 in the μM range in inhibiting the targeted protein kinase. CONCLUSION Further optimization of compounds in this series is currently being carried out. The encouraging preliminary results have revealed potential novel strategies for inhibiting kinase activity for the treatment of medulloblastoma.