Tryptophan-derived Alkaloids from Hedera rhombea Fruits and Their Butyrylcholinesterase Inhibitory Activity

Abstract

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease in industrialized countries. It is estimated that about 47 million people living with dementia and the number of cases will be tripled by 2050. However, the exact mechanism of AD is not known, and full therapy has still not been found. Various tryptophan-derived alkaloids have been reported as promising agents for the treatment of AD. In the present study, a series of tryptophan-derived alkaloids were isolated and characterized from the methanol extract of Hedera rhombea fruit. Based on the analysis of their observed and reported spectroscopic data, their structures were identified as N-[4′-hydroxy-(E)-cinnamoyl]-L-tryptophan (1), N-[3′,4′-dihydroxy-(E)-cinnamoyl]-L-tryptophan (2), N-[4′-hydroxy-(E)-cinnamoyl]-L-tryptophan methyl ester (3), and N-[3′,4′-dihydroxy-(E)-cinnamoyl]-L-tryptophan methyl ester (4). These compounds were screened for anti-Alzheimer activity via their inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in vitro. As a result, compounds 3 and 4 showed moderate BChE inhibition with ICSUB50 /SUBvalues of 86.9 and 78.4 μM, respectively, compared to those of the positive control [berberine (IC50 = 11.5 μM)]. However, all four compounds did not show significant inhibition of the AChE enzyme. This is the first time, the AChE and BChE inhibitory activities of these tryptophan-derived alkaloids were investigated and reported.