Nitrogen-containing flavonoid and their analogs with diverse B-ring in acetylcholinesterase and butyrylcholinesterase inhibition
Autor: | Qian‐Fan Zhang, Ya‐Ming Chen, Xing Feng, Jian‐Ye Yan, Xiao-Hui Gao, Ying‐Zi Liu, Haoran Liu, Pei‐Wu Cui, Qiao‐Qiao Lu |
---|---|
Rok vydání: | 2019 |
Předmět: |
chemistry.chemical_classification
biology Tertiary amine Stereochemistry Biological activity Acetylcholinesterase Flavones 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry 030220 oncology & carcinogenesis Drug Discovery Chromone biology.protein Structure–activity relationship 030217 neurology & neurosurgery Butyrylcholinesterase Cholinesterase |
Zdroj: | Drug development researchREFERENCES. |
ISSN: | 1098-2299 |
Popis: | 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 (IC50 = 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. |
Databáze: | OpenAIRE |
Externí odkaz: |