Discovery of efficient stimulators for adult hippocampal neurogenesis based on scaffolds in dragon's blood

Reduction of hippocampal neurogenesis caused by aging and neurological disorders would impair neural circuits and result in memory loss. A new lead compound (N-trans-3′,4'-methylenedioxystilben-4-yl acetamide 27) has been discovered to efficiently stimulate adult rats' neurogenesis. In-dep...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2017-08, Vol.136, p.382-392
Main Authors: Liang, Jian-Hua, Yang, Liang, Wu, Si, Liu, Si-Si, Cushman, Mark, Tian, Jing, Li, Nuo-Min, Yang, Qing-Hu, Zhang, He-Ao, Qiu, Yun-Jie, Xiang, Lin, Ma, Cong-Xuan, Li, Xue-Meng, Qing, Hong
Format: Article
Language:English
Subjects:
Acetanilides - chemistry
Acetanilides - isolation & purification
Acetanilides - pharmacology
Animals
BrdU
Cell Line, Tumor
Cell Survival - drug effects
Dose-Response Relationship, Drug
Dragon's blood
Drug Discovery
Hippocampus - drug effects
Humans
Male
Molecular Structure
NeuN
Neurogenesis
Neurogenesis - drug effects
Plant Extracts - chemistry
Rats
Rats, Sprague-Dawley
SAR
Stilbene
Stilbenes - chemistry
Stilbenes - isolation & purification
Stilbenes - pharmacology
Structure-Activity Relationship
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Summary:Reduction of hippocampal neurogenesis caused by aging and neurological disorders would impair neural circuits and result in memory loss. A new lead compound (N-trans-3′,4'-methylenedioxystilben-4-yl acetamide 27) has been discovered to efficiently stimulate adult rats' neurogenesis. In-depth structure-activity relationship studies proved the necessity of a stilbene scaffold that is absent in highly cytotoxic analogs such as chalcones and heteroaryl rings and inactive analogs such as diphenyl acetylene and diphenyl ethane, and validated the importance of an NH in the carboxamide and a methylenedioxy substituent on the benzene ring. Immunohistochemical staining and biochemical analysis indicate, in contrast to previously reported neuroprotective chemicals, N-stilbenyl carboxamides have extra capacity for neuroproliferation-type neurogenesis, thereby providing a foundation for improving the plasticity of the adult mammalian brain. N-stilbenyl carboxamides are discovered as novel and efficient stimulators with the capacity of promoting neuroproliferation-type neurogenesis at sub-milligram per kg doses. [Display omitted] •Certain N-stilbenyl carboxamides promote neuroproliferation-type neurogenesis.•Certain N-stilbenyl carboxamides are effective at low doses of sub-milligram per kg.•N-Stilbenyl carboxamides are achiral and readily accessible.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2017.05.025