%0 Journal Article
%T Novel cinnamic acid-tryptamine hybrids as potent butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study.
%A Ghafary S
%A Najafi Z
%A Mohammadi-Khanaposhtani M
%A Nadri H
%A Edraki N
%A Ayashi N
%A Larijani B
%A Amini M
%A Mahdavi M
%J Arch Pharm (Weinheim)
%V 351
%N 10
%D Oct 2018
%M 30284339
%F 4.613
%R 10.1002/ardp.201800115
%X A novel series of cinnamic acid-tryptamine hybrids was designed, synthesized, and evaluated as cholinesterase inhibitors. Anticholinesterase assays showed that all of the synthesized compounds displayed a clearly selective inhibition of butyrylcholinesterase (BChE), but only a moderate inhibitory effect toward acetylcholinesterase (AChE) was detected. Among these cinnamic acid-tryptamine hybrids, compound 7d was found to be the most potent inhibitor of BChE with an IC50 value of 0.55 ± 0.04 μM. This compound showed a 14-fold higher inhibitory potency than the standard drug donepezil (IC50  = 7.79 ± 0.81 μM) and inhibited BChE through a mixed-type inhibition mode. Moreover, a docking study revealed that compound 7d binds to both the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of BChE. Also, compound 7d was evaluated against β-secretase, which exhibited low activity (inhibition percentage: 38%).