Enzyme Kinetics and Molecular Docking Investigation of Acetylcholinesterase and Butyrylcholinesterase Inhibitors from the Marine Alga Ecklonia cava

Ecklonia cava Kjellman (Laminareaceae) grows along the coast of Jeju Island, Korea, and is well-known in Korea for its use as a food ingredient, animal feed, and medicine. This seaweed contains phlorotannins, polymerized units of phloroglucinol, a term derived from phloroglucinol, the building block of these complex molecules, which is also the common name for these compounds. Phlorotannins are secondary metabolites that hold significance for human health due to their various beneficial properties, including antioxidant, anti-cancer, anti-allergy, and anti-HIV activities. In this study, 10 phlorotannins (1–10) were isolated from an 80% EtOH extract of E. cava. The structures of these compounds were determined through spectroscopic analysis and comparison with the literature. The inhibitory effects of compounds 1–10 on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were investigated. In an AChE inhibition assay, compounds 1, 2, 4, and 6–10 had IC₅₀ values ranging from 0.9 ± 0.8 to 66.5 ± 0.4 µM; compounds 4, 6, and 9 had potent BuChE inhibitory effects, with IC₅₀ values ranging from 1.4 ± 3.8 to 25.2 ± 0.1 µM. Furthermore, enzyme kinetics and molecular docking simulations were conducted to gain insights into the inhibition mode, binding mechanism, and crucial interactions between these active compounds and the target enzyme. This indicates that E. cava is a potentially valuable natural source of AChE and BuChE inhibitors.