These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Isosteroidal alkaloids as potent dual-binding site inhibitors of both acetylcholinesterase and butyrylcholinesterase from the bulbs of Fritillaria walujewii.
    Author: Liu YM, Feng YD, Lu X, Nie JB, Li W, Wang LN, Tian LJ, Liu QH.
    Journal: Eur J Med Chem; 2017 Sep 08; 137():280-291. PubMed ID: 28605675.
    Abstract:
    Five new isosteroidal alkaloids, walujewine A (1), walujewine B (4), walujewine C (5), walujewine D (6), walujewine E (10) were isolated from the bulbs of Fritillaria walujewii together with seven known isosteroidal alkaloids (2, 3, 7-9, 11, 12). Their structures were elucidated on the basis of IR, ESI-MS, HR-ESI-MS, 1D and 2D NMR spectroscopic data analyses and single-crystal X-ray diffraction. All the isolates were tested for ChE inhibiting activity by the Ellman's method. Compounds 3-5 and 8-10 were potent dual AChE-BChE inhibitors, and compound 1 showed highly selective AChE inhibition. The structure-activity relationship of compounds 1-12 was discussed in details. And kinetic analysis showed that compounds 1, 3-5, and 8-10 were mixed-type reversible inhibitors of AChE, simultaneously binding to the catalytic and peripheral anionic sites, which was verified by in silico docking studies. The docking simulation also showed that active compound 3 and 8 created many interactions with the CAS and PAS gorges of BChE, revealing their mixed-type inhibition. ADMET analysis further confirmed the therapeutic potential of some isosteroidal alkaloids based on their high BBB-penetration.
    [Abstract] [Full Text] [Related] [New Search]