New coumarin hybrids with antiproliferative activity against a neuroblastoma cell line

In order to identify new agents endowed with antiproliferative activity, our research project aims to design and synthesize new hybrid molecules using the fragment-based strategy. For this purpose, two naturally occurring scaffolds with antiproliferative and antioxidant properties were combined hoping for a synergistic effect. We decided to synthesize new hydrazones of coumarin-3-carboxylic acid with phenoxy- or benzyloxy-substituted vanillin or isovanillin, obtaining a small library of compounds throughout multistep synthesis in good yields. To evaluate the antioxidant properties depending on chemical structure, all the compounds were tested through the DPPH colourimetric assay. Furthermore, the compounds were tested for their antiproliferative activity both on a neuroblastoma cell line (HTLA-230) and an etoposide-resistant one (HTLA-230-ER)1. The IC50 values were determined by MTT assay and results showed a low μM activity for some of these compounds. It is interesting to note that in most cases, the activity is similar both against the normal neuroblastoma cell line as well as on the resistant one. Additional tests on compounds with the best antiproliferative activity are being carried out to evaluate the antioxidant activity in cellular assays (inhibition of reactive oxygen species (ROS) production). Overall, the results will allow us to highlight the importance of the antioxidant activity of the new compounds and further studies will clarify the presence of possible additional mechanisms of action.