Furofuranoid-Type Lignans and Related Phenolics from (Salisb.) Nees with Promising Anticholinesterase and Anti-Ageing Properties: A Study Supported by Molecular Modelling.

Lignan phytomolecules demonstrate promising anti-Alzheimer activity by alleviating dementia and preserving nerve cells. The purpose of this work is to characterize the lignans of and explore their potential anti-acetylcholinesterase and anti-ageing effects. Phytochemical investigation of aerial parts afforded a new furofuranoid-type lignan (), four known structural analogues, namely pinoresinol (), epipinoresinol (), phillyrin (), and pinoresinol 4---d-glucoside (), in addition to -methoxy--methyl cinnamate () and 1H-indole-3-carboxaldehyde (). The structures were established from thorough spectroscopic analyses and comparisons with the literature. Assessment of the anticholinesterase activity of the lignans - displayed noticeable enzyme inhibition of (IC = 85.03 ± 4.26 nM) and (64.47 ± 2.75 nM) but lower activity of compounds - as compared to the reference drug donepezil. These findings were further emphasized by molecular docking of and with acetylcholinesterase (AChE). Rapid overlay chemical similarity (ROCS) and structure-activity relationships (SAR) analysis highlighted and rationalized the anti-AD capability of these compounds. Telomerase activation testing of the same isolates revealed 1.64-, 1.66-, and 1.72-fold activations in cells treated with compounds , , and , respectively, compared to untreated cells. Our findings may pave the way for further investigations into the development of anti-Alzheimer and/or anti-ageing drugs from furofuranoid-type lignans.