Synthesis, molecular docking, and biological evaluation of novel 2-pyrazoline derivatives as multifunctional agents for the treatment of Alzheimer's disease.

ABSTRACT: A novel series of 2-pyrazoline derivatives were designed, synthesized, and evaluated for cholinesterase (ChE) inhibitory, Aβ anti-aggregating and neuroprotective activities. Among these, 3d, 3e, 3g, and 3h were established as the most potent and selective BChE inhibitors (IC₅₀ = 0.5-3.9 μM), while 3f presented dual inhibitory activity against BChE and AChE (IC₅₀ = 6.0 and 6.5 μM, respectively). Kinetic analyses revealed that 3g is a partial noncompetitive inhibitor of BChE (Ki = 2.22 μM), while 3f exerts competitive inhibition on AChE (Ki = 0.63 μM). The active compounds were subsequently screened for further assessments. 3f, 3g and 3h reduced Aβ_1-42 aggregation levels significantly (72.6

SUBMITTER: Unsal-Tan O 

PROVIDER: S-EPMC6596387 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature