Nrf2-ARE/hMAO-B/QR2 modulator 1, a new resveratrol-based multitarget-directed ligand (MTDL), exhibits a well-balanced MTDL profile: it activates the NRF2-ARE pathway (CD = 9.83 μM), selectively inhibits both hMAO-B and QR2 (IC50s = 8.05 and 0.57 μM), and effectively promotes hippocampal neurogenesis. It exerts neuroprotective and antioxidant actions in both acute and chronic Alzheimer models using hippocampal tissues.

Nrf2-ARE/hMAO-B/QR2 modulator 1 (compound 4e) (100 μM; 24 hours) reduces SH-SY5Y cell viability by approximately 30% in the MTT assay[1]. When pre-treated at 1 μM for 24 hours and then coincubated for another 24 hours with 10 nM okadaic acid (OA), it significantly increases cell viability of OA-treated rat primary cortical neurons to 70-80%, counteracting the 50% viability reduction caused by OA alone[1]. At 10 μM, it exhibits the highest expression of young cells (TuJ-1) and mature neurons (MAP-2), and the greatest cell migration distance, indicating strong neurogenic potential[1]. Additionally, at 1 μM for 72 hours, it provides neuroprotection, reduces cell death, and significantly decreases ROS production in mouse hippocampal slices exposed to OA[1].