Burčul Franko, Generalić Mekinić Ivana, Radan Mila, Rollin Patrick, Blažević Ivica
a Department of Analytical Chemistry, Faculty of Chemistry and Technology , University of Split , Split , Croatia.
b Department of Food Technology and Biotechnology, Faculty of Chemistry and Technology , University of Split , Split , Croatia.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):577-582. doi: 10.1080/14756366.2018.1442832.
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 IC 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.
寻找一种新型胆碱酯酶抑制剂，以克服脑内可用性、药代动力学参数或肝毒性问题，一直是阿尔茨海默病治疗研究的重点。异硫氰酸盐此前尚未作为潜在的胆碱酯酶抑制剂进行研究。这些化合物可由其硫代葡萄糖苷前体天然产生，硫代葡萄糖苷是广泛分布于我们日常食用的十字花科蔬菜中的次生代谢产物。在11种受试化合物中，苯基异硫氰酸盐及其衍生物表现出最具前景的抑制活性。2-甲氧基苯基异硫氰酸酯对乙酰胆碱酯酶的抑制作用最佳，IC50为0.57 mM，而3-甲氧基苯基异硫氰酸酯对丁酰胆碱酯酶的抑制作用最佳，在1.14 mM时抑制率为49.2%。使用不同方法评估抗氧化功效得出了类似结论。还使用人COX-2酶测试了抗炎活性，苯基异硫氰酸酯和3-甲氧基苯基异硫氰酸酯活性最高，在50 μM时抑制率约为99%。
