New acetylcholinesterase inhibitors isolated from Delphinium uncinatum

• Published in: Arabian Journal of Chemistry
• Main Author: Gul N.; Ahmad S.; Ahmad H.; Aziz A.; Almehmadi M.; Amer Alsaiari A.; Allahyani M.; Zainab; Adnan Ali Shah S.; Ur Rahman N.; Ahmad M.
• Format: Article
• Language: English
• Published: Elsevier B.V. 2023
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85141922364&doi=10.1016%2fj.arabjc.2022.104408&partnerID=40&md5=a658ef73f33f23017246ade70eb1869d

The inhibition of acetylcholinesterase (AChE), the key enzyme in the breakdown of acetylcholine, is presently the most common pharmacological approach available for Alzheimer's disease (AD). Despite research on the molecular bases of AD, potent therapeutic agent against its expansion is still needed. In searching for natural cholinesterase inhibitors, the present study was focused on the isolation of three new norditerpenoid alkaloids, uncinatine B-D together with known virescenine from Delphinium uncinatum. Chemical structures for all the isolated norditerpenoids (1–4) were established using latest spectroscopic techniques. The isolated undescribed compounds along with known virescenine were testified for their acetylcholinesterase inhibitory activity supported by docking analyses. Molecular docking simulation showed that the isolated compounds (1–4) were observed to adhered in the active site of AChE with docking scores − 13.5322 (1), −11.8173 (2), −12.4240 (3) and − 8.9352 (4) respectively. Overall results demonstrated that these natural norditerpenoids compounds were found as selective inhibitors of AChE. This is the first report regarding the use of bioactive ingredients of Delphinium uncinatum in testing against Alzheimer's disease. © 2022 The Author(s)