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Tryptamine–Triazole Hybrid Compounds for Selective Butyrylcholinesterase Inhibition
Author(s) -
Son Minky,
Lee Haneul,
Jeon Cheolmin,
Kang Yujung,
Park Chanin,
Lee Keun Woo,
Park Jeong Ho
Publication year - 2019
Publication title -
bulletin of the korean chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.237
H-Index - 59
ISSN - 1229-5949
DOI - 10.1002/bkcs.11729
Subject(s) - butyrylcholinesterase , tryptamine , chemistry , azide , acetylcholinesterase , stereochemistry , cholinesterase , oxyanion hole , triazole , active site , molecular model , enzyme , organic chemistry , aché , biochemistry , pharmacology , medicine
Tryptamine–triazole hybrid compounds ( 11 – 18 ) were synthesized via click reaction between tryptamine azide and propargylated natural compounds. Their cholinesterase inhibitory activity was evaluated. Among the eight compounds, compound 11 showed the most potent inhibitory activity [IC 50 = 0.42 ± 0.29 μM for equine butyrylcholinesterase (BuChE) and 1.96 ± 0.15 μM for human BuChE]. From the molecular modeling study, compound 11 was bound to the catalytic anionic site, anionic subsite, peripheral anionic subsite, acyl‐binding pocket, and oxyanion hole of human or horse BuChE by forming a hairpin or U‐shaped structure. The Lineweaver‐Burk plot of compound 11 against BuChE suggests a mixed type of inhibition which corresponds well with the molecular modeling study.