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- Title
Discovery of Novel Diphenyl Acrylonitrile Derivatives That Promote Adult Rats' Hippocampal Neurogenesis.
- Authors
Liu, Si-Si; Ma, Cong-Xuan; Quan, Zheng-Yang; Ding, Jing; Yang, Liang; Liu, Si-Meng; Zhang, He-Ao; Qing, Hong; Liang, Jian-Hua
- Abstract
We previously discovered WS-6 as a new antidepressant in correlation to its function of stimulating neurogenesis. Herein, several different scaffolds (stilbene, 1,3-diphenyl 1-propene, 1,3-diphenyl 2-propene, 1,2-diphenyl acrylo-1-nitrile, 1,2-diphenyl acrylo-2-nitrile, 1,3-diphenyl trimethylamine), further varied through substitutions of twelve amide substituents plus the addition of a methylene unit and an inverted amide, were examined to elucidate the SARs for promoting adult rat neurogenesis. Most of the compounds could stimulate proliferation of progenitors, but just a few chemicals possessing a specific structural profile, exemplified by diphenyl acrylonitrile 29b, 32a, and 32b, showed better activity than the clinical drug NSI-189 in promoting newborn cells differentiation into mature neurons. The most potent diphenyl acrylonitrile 32b had an excellent brain AUC to plasma AUC ratio (B/P = 1.6), suggesting its potential for further development as a new lead.
- Subjects
ACRYLONITRILE; DIPHENYL; NEUROGENESIS; CELL differentiation; HIPPOCAMPUS (Brain); TRIMETHYLAMINE oxide
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 2, p1241
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25021241