Isothiocyanates: cholinesterase inhibiting, antioxidant, and anti-inflammatory activity.

J Enzyme Inhib Med Chem. 2018 Dec;33(1):577-582. doi: 10.1080/14756366.2018.1442832. Burčul F1, Generalić Mekinić I2, Radan M3, Rollin P4, Blažević I5. Author information 1 a Department of Analytical Chemistry, Faculty of Chemistry and Technology , University of Split , Split , Croatia. 2 b Department of Food Technology and Biotechnology, Faculty of Chemistry and Technology , University of Split , Split , Croatia. 3 c Department of Biochemistry, Faculty of Chemistry and Technology , University of Split , Split , Croatia. 4 d ICOA, UMR 7311, Université d'Orléans et CNRS , Orléans , France. 5 e Department of Organic Chemistry, Faculty of Chemistry and Technology , University of Split , Split , Croatia. Abstract Finding a new type of cholinesterase inhibitor that would overcome the brain availability and pharmacokinetic parameters or hepatotoxic liability has been a focus of investigations dealing with the treatment of Alzheimer's disease. Isothiocyanates have not been previously investigated as potential cholinesterase inhibitors. These compounds can be naturally produced from their glucosinolate precursors, secondary metabolites widely distributed in our daily Brassica vegetables. Among 11 tested compounds, phenyl isothiocyanate and its derivatives showed the most promising inhibitory activity. 2-Methoxyphenyl ITC showed best inhibition on acetylcholinesterase with IC50 of 0.57 mM, while 3-methoxyphenyl ITC showed the best inhibition on butyrylcholinesterase having 49.2% at 1.14 mM. Assessment of the antioxidant efficacy using different methods led to a similar conclusion. The anti-inflammatory activity was also tested using human COX-2 enzyme, ranking phenyl isothiocyanate, and 3-methoxyphenyl isothiocyanate as most active, with ∼99% inhibition at 50 μM. KEYWORDS: Isothiocyanates; anti-inflammatory activity; antioxidation; cholinesterase inhibition PMID: 29513045 PMCID: PMC6010089 DOI: 10.1080/14756366.2018.1442832 [Indexed for MEDLINE] Free PMC Article