Khelifi_2020_Biotechnol.Appl.Biochem_67_983

Alzheimer's disease is characterized by amyloid beta aggregation and cholinergic neurodegeneration. In the present study, pure DDN (2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone) was examined, for the first time, for its dual potential as inhibitor of acetylcholinesterase (AChE) and Abeta(42) aggregation. Such investigation was encouraged by the in vitro high antioxidant potential of DDN. Indeed, it revealed interesting antioxidant activity with IC(50) values of 9.8 and 4.3 microM for ABTS and reducing power, respectively. The ability of DDN to counteract Abeta(42) aggregation was evaluated by thioflavine-T assay. Strong inhibition of Abeta(42) aggregation of more than 90% at 25 microM was measured. Moreover, results showed that DDN inhibited AChE (IC(50) = 14.5 microM). To better understand the interactions between DDN and AChE, molecular docking was performed. Obtained data predicted a high interaction characterized by hydrogen bonding at TYR337 as for galanthamine (positive control). Several residues involved in AChE hydrophobic interactions were similarly implicated in binding of this domain to DDN (ASP74, THR83, and TYR124). All these data would be useless if DDN could not pass the blood-brain barrier. So, DDN was loaded into alginate microspheres to enhance its stability and bioavailability. Thereafter, drug release profiles were assessed using immersion cell apparatus.