http://www.sciencedirect.com/science/article/pii/S0223523417303860
Highlights
- •
- Certain N-stilbenyl carboxamides promote neuroproliferation-type neurogenesis.
- •
- Certain N-stilbenyl carboxamides are effective at low doses of sub-milligram per kg.
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- N-Stilbenyl carboxamides are achiral and readily accessible.
Abstract
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.
Graphical abstract
Keywords
- Neurogenesis;
- Stilbene;
- SAR;
- Dragon's blood;
- BrdU;
- NeuN
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