Multitarget-Directed Benzylideneindanone Derivatives: Anti-β-Amyloid (Aβ) Aggregation, Antioxidant, Metal Chelation, and Monoamine Oxidase B (MAO-B) Inhibition Properties against Alzheimer’s Disease

A novel series of benzylideneindanone derivatives were designed, synthesized, and evaluated as multitarget-directed ligands against Alzheimer's disease. The in vitro studies showed that most of the molecules exhibited a significant ability to inhibit self-induced β-amyloid (Aβ(1-42)) aggregation (10.5-80.1%, 20 μM) and MAO-B activity (IC(50) of 7.5-40.5 μM), to act as potential antioxidants (ORAC-FL value of 2.75-9.37), and to function as metal chelators. In particular, compound 41 had the greatest ability to inhibit Aβ(1-42) aggregation (80.1%), and MAO-B (IC(50) = 7.5 μM) was also an excellent antioxidant and metal chelator. Moreover, it is capable of inhibiting Cu(II)-induced Aβ(1-42) aggregation and disassembling the well-structured Aβ fibrils. These results indicated that compound 41 is an excellent multifunctional agent for the treatment of AD.