Novel cinnamic acid-tryptamine hybrids as potent butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study.
Arch Pharm (Weinheim)
; 351(10): e1800115, 2018 Oct.
Article
in En
| MEDLINE
| ID: mdl-30284339
ABSTRACT
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 ß-secretase, which exhibited low activity (inhibition percentage 38%).
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acetylcholinesterase
/
Butyrylcholinesterase
/
Tryptamines
/
Cholinesterase Inhibitors
/
Cinnamates
/
Neuroprotective Agents
/
Molecular Docking Simulation
Limits:
Animals
Language:
En
Journal:
Arch Pharm (Weinheim)
Year:
2018
Type:
Article
Affiliation country:
Iran