In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from Delphinium chitralense

• Published in: Molecules
• Main Author: Ahmad S.; Ahmad M.; Almehmadi M.; Shah S.A.A.; Khan F.A.; Khan N.M.; Khan A.; Zainab; Halawi M.; Ahmad H.
• Format: Article
• Language: English
• Published: MDPI 2022
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85135133296&doi=10.3390%2fmolecules27144348&partnerID=40&md5=a453b3fe8b1ecd9b1ac29dfb646599f2

This study reports the isolation of three new C20 diterpenoid alkaloids, Chitralinine A–C (1–3) from the aerial parts of Delphinium chitralense. Their structures were established on the basis of latest spectral techniques and single crystal X-rays crystallographic studies of chitralinine A described basic skeleton of these compounds. All the isolated Compounds (1–3) showed strong, competitive type inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in comparison to standard allanzanthane and galanthamine however, chitralinine-C remained the most potent with IC50 value of 11.64 ± 0.08 μM against AChE, and 24.31 ± 0.33 μM against BChE, respectively. The molecular docking reflected a binding free energy of −16.400 K Cal-mol−1 for chitralinine-C, having strong interactions with active site residues, TYR334, ASP72, SER122, and SER200. The overall findings suggest that these new diterpenoid alkaloids could serve as lead drugs against dementia-related diseases including Alzheimer’s disease. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. All rights reserved.