Nrf2-ARE/hMAO-B/QR2 modulator 1 is a new resveratrol-based multitarget-directed ligands (MTDLs) that showed a well-balanced MTDL profile: cellular activation of the NRF2-ARE pathway (CD = 9.83 μM), selective inhibition of both hMAO-B and QR2 (IC50s = 8.05 and 0.57 μM), and the best ability to promote hippocampal neurogenesis. Nrf2-ARE/hMAO-B/QR2 modulator 1 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 the viability of SH-SY5Y cells by around 30% in MTT assay[1]. Nrf2-ARE/hMAO-B/QR2 modulator 1 (1 μM; 24 hours for pre-treatment, then coincubated for another 24 hours with 10 nM okadaic acid (OA)) significantly increases the cell viability of OA-treated rat primary cortical neurons to 70-80% while OA (10 nM) reduced the cell viability by 50%[1]. Nrf2-ARE/hMAO-B/QR2 modulator 1 (10 μM) shows the highest expression of young cells (TuJ-1) and mature neurons (MAP-2), as well as the greatest distance of cell migration which indicate that this compound has a great neurogenic potential due to its ability to promote different aspects involved in neurogenesis[1]. Nrf2-ARE/hMAO-B/QR2 modulator 1 (1 μM; 72 hours) confers neuroprotection and reduces cell death, significantly reduces ROS production in mice hippocampal slices exposed to OA [1].