1 Department of Pharmacognosy, College of Pharmacy, Najran University, Najran 55461, Saudi Arabia. Electronic address: maorabi@nu.edu.sa.
2 Department of Chemistry and Biochemistry, Concordia University, 7141 Sherbrooke Street West, Montréal, Québec H4B 1R6, Canada.
3 Department of Medical Microbiology and Immunology, Faculty of Pharmacy, South Valley University, Qena 83523, Egypt.
4 Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Tsushima, Kita-Ku, Okayama 700-8530, Japan.
5 Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City 32958, Egypt; Department of Biochemistry, Faculty of Pharmacy, Sinai University, Kantara, Egypt.

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 ?-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 ¹H¹H 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; IC₅₀ = 34 ± 2 nM) and stachyurin (8; IC₅₀ = 56 ± 3 nM)], and the new dimer (2; IC₅₀ = 61 ± 4 nM) possess enzyme inhibitory effects comparable to the reference drug (donepezil, IC₅₀ = 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.