Acetylcholinesterase as a target of halogenated marine natural products from Laurencia dendroidea

The use of chemogenomics techniques applied to a marine natural products database has pointed out halogenated sesquiterpenes present in red alga Laurencia dendroidea as potential acetylcholinesterase inhibitors. Therefore, in this work five metabolites were studied using molecular docking and enzymatic inhibition assays. According to the results the most promising metabolite in relation to acetylcholinesterase inhibition capacity was (−)-elatol 1. Molecular docking of (−)-elatol 1 showed interactions with important specific residues of the enzyme gorge involved in the activity of drugs used to treat Alzheimer's disease. In this respect, interactions between halogens bromine and chlorine with the center of the benzene ring of Tryptophan 86 and Tryptophan 286 may be contributing to the observed activity. Enzyme kinetics was investigated to find out the type of enzyme inhibition involved in the observed activities. Results have also shown stereochemical preferences related to the inhibition by halogenated compounds. (−)-Elatol 1 was able to inhibit acetylcholinesterase, thus becoming a suitable skeleton in the search for new anti-Alzheimer drugs of natural and semi-synthetic origin.