Design, Synthesis of N-phenethyl Cinnamide Derivatives and Their Biological Activities for the Treatment of Alzheimer’s Disease: Antioxidant, Beta-amyloid Disaggregating and Rescue Effects on Memory Loss
Tian Chai,
Xiao-Bo Zhao,
Wei-Feng Wang,
Yin Qiang,
Xiao-Yun Zhang,
Jun-Li Yang
Affiliations
Tian Chai
School of Pharmacy, Lanzhou University, Lanzhou 730000, China
Xiao-Bo Zhao
CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences (CAS), Lanzhou 730000, China
Wei-Feng Wang
CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences (CAS), Lanzhou 730000, China
Yin Qiang
School of Pharmacy, Lanzhou University, Lanzhou 730000, China
Xiao-Yun Zhang
School of Pharmacy, Lanzhou University, Lanzhou 730000, China
Jun-Li Yang
CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences (CAS), Lanzhou 730000, China
Gx-50 is a bioactive compound for the treatment of Alzheimer’s disease (AD) found in Sichuan pepper (Zanthoxylum bungeanum). In order to find a stronger anti-AD lead compound, 20 gx-50 (1–20) analogs have been designed and synthesized, and their molecular structures were determined based on nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis, as well as comparison with literature data. Compounds 1–20 were evaluated for their anti-AD potential by using DPPH radical scavenging assay for considering their anti-oxidant activity, thioflavin T (ThT) fluorescence assay for considering the inhibitory or disaggregate potency of Aβ, and transgenic Drosophila model assay for evaluating their rescue effect on memory loss. Finally, compound 13 was determined as a promising anti-AD candidate.
