Discovery of Novel Diphenyl Acrylonitrile Derivatives That Promote Adult Rats’ Hippocampal Neurogenesis

Si Si Liu, Cong Xuan Ma, Zheng Yang Quan, Jing Ding, Liang Yang, Si Meng Liu, He Ao Zhang, Hong Qing*, Jian Hua Liang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number1241
JournalInternational Journal of Molecular Sciences
Volume25
Issue number2
DOIs
Publication statusPublished - Jan 2024

Keywords

  • SARs
  • differentiation
  • diphenyl acrylonitrile
  • neurogenesis
  • proliferation

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