In industrialized countries, Alzheimer's disease represents the most devastating neurodegenerative
disorder in elderly people and the search for a disease modifying agent is still justified by
this unmet need. Several possible targets have been explored to find an appropriate drug therapy, and
in this review, dual inhibitors of beta secretase and glycogen synthase kinase 3, recently reported in
literature, will be appraised. Applying a ligand-based approach, the triazinone core emerged as a suitable
scaffold to simultaneously bind the aspartic dyad of BACE-1 and the ATP site of GSK-3β, leading
to a series of small molecules endowed with a balanced micromolar affinity and a promising
Differently, by means of a structure-based approach, a series of well-balanced dual binding molecules
were designed, taking advantage of the versatility of the curcumin scaffold. For some of these new
compounds a potential neuroprotective effect was also observed, due to their ability to counteract the
oxidative stress through the inhibition of NQO1 enzyme.
Finally, different virtual screening analyses were performed, leading to the identification of new potential
scaffolds deserving further development.