Norditerpenoid alkaloids of Delphinium denudatum as cholinesterase inhibitors

• Published in: Bioorganic Chemistry
• Main Author: Ahmad H.; Ahmad S.; Ali M.; Latif A.; Shah S.A.A.; Naz H.; ur Rahman N.; Shaheen F.; Wadood A.; Khan H.U.; Ahmad M.
• Format: Article
• Language: English
• Published: Academic Press Inc. 2018
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85046358282&doi=10.1016%2fj.bioorg.2018.04.008&partnerID=40&md5=62c22232210c840358840c2006948b1a

Three new norditerpenoids alkaloids, 1β-hydroxy,14β-acetyl condelphine (1), jadwarine-A (2), jadwarine-B (3) along with two known alkaloids isotalatizidine hydrate (4) and dihydropentagynine (5) were isolated from medicinal plant Delphinium denudatum. The structures of natural products 1–5 were established on the basis of HR-EIMS, 1H and 13C NMR (1D & 2D) spectroscopic data as well as by comparison from literature data. The structures of compound 1 and 4 were also confirmed by single crystal X-ray diffraction studies. In-vitro AChE and BChE enzyme inhibitory activities of compounds 1–5 and molecular docking studies were performed to investigate the possible molecular inhibitory mechanism of the isolated natural products. Compound 2, 4 and 5 showed competitive inhibitory effects by inhibiting AChE and BChE, respectively, while 1 and 3 showed non-competitive inhibition. This work is the first report that provides a supporting evidence about the use of constituents of Delphinium denudatum in cerebral dementia and Alzheimer diseases. © 2018 Elsevier Inc.