Multitarget-Directed Benzylideneindanone\nDerivatives:\nAnti-β-Amyloid (Aβ) Aggregation, Antioxidant, Metal Chelation,\nand Monoamine Oxidase B (MAO-B) Inhibition Properties against Alzheimer’s\nDisease

Abstract

A novel series of benzylideneindanone derivatives were\ndesigned,\nsynthesized, and evaluated as multitarget-directed ligands against\nAlzheimer’s disease. The in vitro studies showed that most\nof the molecules exhibited a significant ability to inhibit self-induced\nβ-amyloid (Aβ_1–42) aggregation (10.5–80.1%,\n20 μM) and MAO-B activity (IC₅₀ of 7.5–40.5\nμM), to act as potential antioxidants (ORAC-FL value of 2.75–9.37),\nand to function as metal chelators. In particular, compound <b>41</b> had the greatest ability to inhibit Aβ_1–42 aggregation (80.1%), and MAO-B (IC₅₀ =\n7.5 μM) was also an excellent antioxidant and metal chelator.\nMoreover, it is capable of inhibiting Cu­(II)-induced Aβ_1–42 aggregation and disassembling the well-structured\nAβ fibrils. These results indicated that compound <b>41</b> is an excellent multifunctional agent for the treatment of AD.