Development of novel N-(6-methanesulfonyl-benzothiazol-2-yl)-3-(4-substituted-piperazin-1-yl)-propionamides with cholinesterase inhibition, anti-β-amyloid aggregation, neuroprotection and cognition enhancing properties for the therapy of Alzheimer's disease.

ABSTRACT: A novel series of benzothiazole-piperazine hybrids were rationally designed, synthesized, and evaluated as multifunctional ligands against Alzheimer's disease (AD). The synthesized hybrid molecules illustrated modest to strong inhibition of acetylcholinesterase (AChE) and Aβ_1-42 aggregation. Compound 12 emerged as the most potent hybrid molecule exhibiting balanced functions with effective, uncompetitive and selective inhibition against AChE (IC₅₀ = 2.31 μM), good copper chelation, Aβ_1-42 aggregation inhibition (53.30%) and disaggregation activities. Confocal laser scanning microscopy and TEM analysis also validate the Aβ fibril inhibition ability of this compound. Furthermore, this compound has also shown low toxicity and is capable of impeding loss of cel

SUBMITTER: Mishra CB 

PROVIDER: S-EPMC9053591 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature