Design, synthesis, and neuroprotective activity of salidroside-based dual inhibitors of selective monoamine oxidase B and amyloid-β aggregation

This study focuses on the design, synthesis, and evaluation of a series of salidroside derivatives (pOBZ-1~pOBZ-11) for their potential as inhibitors of monoamine oxidase B (MAO-B) and amyloid beta (Aβ₄₂) aggregation, and neuroprotective agents. Among the synthesized derivatives, pOBZ-1 and pOBZ-2 exhibited superior MAO-B inhibitory activity compared to salidroside, with notable selectivity over MAO-A. These compounds demonstrated linear competitive inhibition. Additionally, the derivatives effectively inhibited Aβ₄₂ aggregation and protected SH-SY5Y cells from Aβ₄₂ and hydrogen peroxide (H₂O₂)-induced neurotoxicity. The findings suggest that pOBZ-2, in particular, holds promise as a therapeutic candidate for Alzheimer’s disease.

Graphical abstract

Novel dual inhibitors of selective MAO-B/amyloid-β aggregation