Nitric oxide inhibitory daphnane diterpenoids as potential anti-neuroinflammatory agents for AD from the twigs of Trigonostemon thyrsoideus

Feng Liu, Xueyuan Yang, Jun Ma, Yuling Yang, Chunfeng Xie, Muhetaer Tuerhong, Da Qing Jin, Jing Xu, Dongho Lee, Yasushi Ohizumi, Yuanqiang Guo

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The extensive pathology studies revealed that Alzheimer's disease (AD) is closely related to neuroinflammation and anti-neuroinflammatory agents may be potentially useful for the treatment of AD. A continuous search for new nitric oxide (NO) inhibitory compounds as anti-neuroinflammatory agents for AD resulted in the isolation of four new (1−4) and eight known (5−12) daphnane diterpenoids from the twigs of Trigonostemon thyrsoideus. Their structures were elucidated on the basis of extensive nuclear magnetic resonance (NMR) spectroscopic data analysis and the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Compounds 1–4 represent new examples of daphnane diterpenoid orthoesters and 4 features a rare and complex macroring diterpenoid structure. The anti-neuroinflammatory effects were examined by inhibiting NO release in lipopolysaccharide (LPS)-induced murine microglial BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein.

Original languageEnglish
Pages (from-to)149-156
Number of pages8
JournalBioorganic Chemistry
Volume75
DOIs
Publication statusPublished - 2017 Dec 1

Keywords

  • Anti-neuroinflammatory
  • Daphnane diterpenoids
  • Molecular docking
  • NO inhibitors
  • Trigonostemon thyrsoideus

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

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