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Nitrogen‐containing flavonoid and their analogs with diverse B‐ring in acetylcholinesterase and butyrylcholinesterase inhibition
Author(s) -
Lu QiaoQiao,
Chen YaMing,
Liu HaoRan,
Yan JianYe,
Cui PeiWu,
Zhang QianFan,
Gao XiaoHui,
Feng Xing,
Liu YingZi
Publication year - 2020
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21726
Subject(s) - chromone , butyrylcholinesterase , chemistry , acetylcholinesterase , flavones , stereochemistry , amine gas treating , tertiary amine , selectivity , aché , cholinesterase , enzyme , organic chemistry , pharmacology , chromatography , medicine , catalysis
In this study, a series of new flavones (2‐phenyl‐chromone), 2‐naphthyl chromone, 2‐anthryl‐chromone, or 2‐biphenyl‐chromone derivatives containing 6 or 7‐substituted tertiary amine side chain were designed, synthesized, and evaluated in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. The results indicated that the alteration of aromatic ring connecting to chromone scaffold brings about a significant impact on biological activity. Compared with flavones, the inhibitory activity of 2‐naphthyl chromone, 2‐anthryl‐chromone derivatives against AChE significantly decreased, while that of 2‐biphenyl chromone derivatives with 7‐substituted tertiary amine side chain is better than relative flavones derivatives. For all new synthesized compounds, the position of tertiary amine side chain obviously influenced the activity of inhibiting AChE. The results above provide great worthy information for the further development of new AChE inhibitors. Among the newly synthesized compounds, compound 5a is potent in AChE inhibition (IC 50 = 1.29 ± 0.10 μmol/L) with high selectivity for AChE over BChE (selectivity ratio: 27.96). An enzyme kinetic study of compound 5a suggests that it produces a mixed‐type inhibitory effect against AChE.