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- W2292876579 abstract "A series of novel multipotent 2-piperidone derivatives were designed, synthesized and biologically evaluated as chemical agents for the treatment of Alzheimer’s disease (AD). The results showed that most of the target compounds displayed significant potency to inhibit Aβ1–42 self-aggregation. Among them, compound 7q exhibited the best inhibition of Aβ1–42 self-aggregation (59.11% at 20 μM) in a concentration-dependent manner. Additionally, the compounds 6b, 7p and 7q as representatives were found to present anti-inflammation properties in lipopolysaccharide (LPS)-induced microglial BV-2 cells. They could effectively suppress the production of pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6. Meanwhile, compound 7q could prevent the neuronal cell SH-SY5Y death by LPS-stimulated microglia cell activation mediated neurotoxicity. The molecular modeling studies demonstrated that compounds matched the pharmacophore well and had good predicted physicochemical properties and estimated IC50 values. Moreover, compound 7q exerted a good binding to the active site of myeloid differentiation factor 88 (MyD88) through the docking analysis and could interfere with its homodimerization or heterodimerization. Consequently, these compounds emerged as promising candidates for further development of novel multifunctional agents for AD treatment." @default.
- W2292876579 created "2016-06-24" @default.
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- W2292876579 date "2016-04-01" @default.
- W2292876579 modified "2023-09-24" @default.
- W2292876579 title "Design, synthesis, and evaluation of 2-piperidone derivatives for the inhibition of β-amyloid aggregation and inflammation mediated neurotoxicity" @default.
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- W2292876579 doi "https://doi.org/10.1016/j.bmc.2016.03.010" @default.
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