Design, Synthesis, and biological evaluation of pyrazolo-benzothiazole derivatives as a potential therapeutic agent for the treatment of Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative age-related brain which diminishes learning and memory. Two main cholinesterases (ChEs), first acetylcholinesterase (AChE) second one butyrylcholinesterase (BChE) are the major targets to treat this disease. In current study, six novel pyrazolo-benzothiazole analogues were systematically planned, synthesized, biological tested for their ChEs activities, antioxidant, enzyme kinetic, self-induced Aβ modulation, PAMPA-BBB, docking molecular simulation study. Among all derivatives, compound 4a bearing 3,4-dimethoxypyrazolo-benzothiazole was potential inhibitor of AChE (IC50 = 8.69 ± 0.42 µM), modulator good antioxidant property. Docking studies also clearly revealed that fit fully into active sites hAChE.