Design and Synthesis of 2-Substitutedphenyl Benzo[D]Thiazole Derivatives and Their β-Amyloid Aggregation and Cholinesterase Inhibitory Activities

Abstract

The occurrence of amyloid-β (Aβ) and reduced cholinergic tranmission are two major hallmarks of Alzheimer’s disease (AD). Therefore, a series of new 2-phenylbenzo[d]thiazoles substituted with azole/piperazine moieties were designed, synthesized, and evaluated as potential dual inhibitors of Aβ aggregation and cholinesterase (ChE) activities. In vitro studies showed that compound 2m containing an imidazole ring strongly inhibited Aβ_1–40 (49.2%) and Aβ_1-42 aggregation (60.6%). All derivatives exhibited weak inhibitory activities against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Therefore, compound 2m may represent promising therapeutic option for inhibiting Aβ-mediated pathology in AD.