期刊
PHARMACEUTICALS
卷 15, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/ph15030304
关键词
benzylbenzofuran; butyrylcholinesterase inhibitors; docking studies
资金
- University of Cagliari
In this study, a combination of computational and biochemical techniques was used to modify the structure of benzofuran derivatives and identify relevant structural features for butyrylcholinesterase inhibitory activity and selectivity. By introducing a methylene spacer and substituents, a novel selective BChE inhibitor was discovered. 5-bromo-2-(4-hydroxybenzyl)benzofuran 9B exhibited the strongest inhibitory activity. Computational studies confirmed the correlation between the theoretical and experimental binding affinity of the compounds to the BChE protein.
In the present work, we use a merger of computational and biochemical techniques as a rational guideline for structural modification of benzofuran derivatives to find pertinent structural features for the butyrylcholinesterase inhibitory activity and selectivity. Previously, we revealed a series of 2-phenylbenzofuran compounds that displayed a selective inhibitory activity for BChE. Here, in an effort to discover novel selective BChE inhibitors with favorable physicochemical and pharmacokinetic profiles, 2-benzylbenzofurans were designed, synthesized, and evaluated as BChE inhibitors. The 2-phenylbenzofuran scaffold structure is modified by introducing one methylene spacer between the benzofuran core and the 2-phenyl ring with a hydroxyl substituent in the para or meta position. Either position 5 or 7 of the benzofuran scaffold was substituted with a bromine or chlorine atom. Further assessment of the selected list of compounds indicated that the substituent's nature and position determined their activity and selectivity. 5-bromo-2-(4-hydroxybenzyl)benzofuran 9B proved to be the most potent butyrylcholinesterase inhibitor (IC50 = 2.93 mu M) of the studied series. Computational studies were carried out to correlate the theoretical and experimental binding affinity of the compounds to the BChE protein.
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