| Title : (-)-Meptazinol-melatonin hybrids as novel dual inhibitors of cholinesterases and amyloid-beta aggregation with high antioxidant potency for Alzheimer's therapy - Cheng_2015_Bioorg.Med.Chem_23_3110 |
| Author(s) : Cheng S , Zheng W , Gong P , Zhou Q , Xie Q , Yu L , Zhang P , Chen L , Li J , Chen J , Chen H |
| Ref : Bioorganic & Medicinal Chemistry , 23 :3110 , 2015 |
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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-beta (Abeta) aggregation and oxidative stress, two prominent neuropathological hallmarks in patients, play crucial roles in the neurotoxic cascade of this disease. In the present study, a series of novel (-)-meptazinol-melatonin hybrids were designed, synthesized and biologically characterized as potential MTDLs against AD. Among them, hybrids 7-7c displayed higher dual inhibitory potency toward cholinesterases (ChEs) and better oxygen radical absorbance capacity (ORAC) than the parental drugs. Furthermore, compound 7c could effectively inhibit Abeta self-aggregation, showed favorable safety and the blood-brain barrier (BBB) permeability. Therefore, 7c may serve as a valuable candidate that is worthy of further investigations in the treatment of AD. |
| PubMedSearch : Cheng_2015_Bioorg.Med.Chem_23_3110 |
| PubMedID: 26025073 |
Cheng S, Zheng W, Gong P, Zhou Q, Xie Q, Yu L, Zhang P, Chen L, Li J, Chen J, Chen H (2015)
(-)-Meptazinol-melatonin hybrids as novel dual inhibitors of cholinesterases and amyloid-beta aggregation with high antioxidant potency for Alzheimer's therapy
Bioorganic & Medicinal Chemistry
23 :3110
Cheng S, Zheng W, Gong P, Zhou Q, Xie Q, Yu L, Zhang P, Chen L, Li J, Chen J, Chen H (2015)
Bioorganic & Medicinal Chemistry
23 :3110