(-)-Meptazinol-melatonin hybrids as novel dual inhibitors of cholinesterases and amyloid-β aggregation with high antioxidant potency for Alzheimer's therapy.
作者： Shaobing Cheng , Wei Zheng , Ping Gong , Qiang Zhou , Qiong Xie
DOI: 10.1016/J.BMC.2015.04.084
关键词: Potency 、 Biochemistry 、 Oxidative stress 、 Chemistry 、 Oxygen radical absorbance capacity 、 Aché 、 5-HT receptor 、 Melatonin 、 Antioxidant 、 Pathogenesis
摘要: Abstract The multifactorial pathogenesis of Alzheimer’s disease (AD) implicates that multi-target-directed ligands (MTDLs) intervention may represent a promising therapy for AD. Amyloid-β (Aβ) aggregation and oxidative stress, two prominent neuropathological hallmarks in patients, play crucial roles the neurotoxic cascade this disease. In present study, series novel (−)-meptazinol–melatonin hybrids were designed, synthesized biologically characterized as potential MTDLs against Among them, 7–7c displayed higher dual inhibitory potency toward cholinesterases (ChEs) better oxygen radical absorbance capacity (ORAC) than parental drugs. Furthermore, compound 7c could effectively inhibit Aβ self-aggregation, showed favorable safety blood–brain barrier (BBB) permeability. Therefore, serve valuable candidate is worthy further investigations treatment
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