Starting from our expertise in the field of the chemical decoration of the coumarin backbone and in the structure-based design of MAO and AChE inhibitors, herein, we described the development of novel multi-target ligands able to potentially improve the cognitive and learning symptoms of AD (by inhibiting AChE), to reduce the production of ROS and ameliorate oxidative stress neuronal conditions through the inhibition of MAO-B activity, taking advantage of a synergy of actions against the disease. Here, MAOB is linked to Alzheimer disease.