Discovery of Sulforaphane as a Potent BACE1 Inhibitor Based on Kinetics and Computational Studies

BACE1 is the rate-limiting enzyme involved in the production and deposition of β-amyloid (Aβ). Since neurotoxic Aβ plays a critical role in Alzheimer’s disease (AD) pathogenesis, BACE1 has emerged as a key target for preventing AD. In the present study, the potential of sulforaphane, an isothiocyanate found in cruciferous vegetables, as a BACE1 inhibitor has been investigated. Sulforaphane exhibited six times more potent activity against BACE1 compared to well-known positive controls including resveratrol and quercetin. Sulforaphane presented selective and non-competitive BACE1 inhibitory activity with low off-target inhibition of BACE2 and other aspartic and serine proteases. In addition, sulforaphane presented negative binding energy, suggesting that the compound had a high affinity for BACE1. It interacted with locations other than the active binding sites of BACE1 through van der Waals forces. Overall, sulforaphane appeared to be a promising candidate with potent and selective BACE1 inhibitory properties that play an important role in AD prevention.