Structural determination and anticholinesterase assay of C-glycosidic ellagitannins from Lawsonia inermis leaves: A study supported by DFT calculations and molecular docking.

An ellagitannin monomer, lythracin M (1), and a dimer, lythracin D (2), along with eight known monomers (3 − 10) were isolated from Lawsonia inermis (Lythraceae) leaves. Lythracin M (1) is a C -glycosidic ellagitannin with a flavogallonyl dilactone moiety that participates in the creation of a γ-lactone ring with the anomeric carbon of the glucose core. Lythracin D (2) was determined as an atropisomer of the reported lythcarin D. These newly discovered structures (1 and 2) were determined by intensive spectroscopic experiments and by comparing DFT-calculated 1H 1H coupling, 1H NMR chemical shifts, and ECD data with experimental values. The anti-acetylcholinesterase assay of the compounds 1 – 10 revealed that the C-1 ellagitannin epimers [casuarinin (7 ; IC 50 = 34 ± 2 nM) and stachyurin (8 ; IC 50 = 56 ± 3 nM)], and the new dimer (2 ; IC 50 = 61 ± 4 nM) possess enzyme inhibitory effects comparable to the reference drug (donepezil, IC 50 = 44 ± 3 nM). Molecular docking of compounds 1 – 10 with AChE identified the free galloyl moiety as an important pharmacophore in the anticholinesterase activity of tannins. [Display omitted] • Two new (1 and 2) and eight known ellagitannins (3 – 10) were isolated from leaves of L. inermis. • The stereo-structure of 1 was established based on DFT calculations and intensive spectroscopic studies. • The anti-AChE activity of 1 – 10 was evaluated experimentally and by using molecular docking. • The ellagitannins 2 , 7 , and 8 are promising anti-AChE. [ABSTRACT FROM AUTHOR]