Structural Insight of New Butyrylcholinesterase Inhibitors Based on Benzylbenzofuran Scaffold

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...

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Bibliographic Details
Main Authors: Giovanna L. Delogu (Author), Antonella Fais (Author), Francesca Pintus (Author), Chinmayi Goyal (Author), Maria J. Matos (Author), Benedetta Era (Author), Amit Kumar (Author)
Format: Book
Published: MDPI AG, 2022-03-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Giovanna L. Delogu  |e author 
700 1 0 |a Antonella Fais  |e author 
700 1 0 |a Francesca Pintus  |e author 
700 1 0 |a Chinmayi Goyal  |e author 
700 1 0 |a Maria J. Matos  |e author 
700 1 0 |a Benedetta Era  |e author 
700 1 0 |a Amit Kumar  |e author 
245 0 0 |a Structural Insight of New Butyrylcholinesterase Inhibitors Based on Benzylbenzofuran Scaffold 
260 |b MDPI AG,   |c 2022-03-01T00:00:00Z. 
500 |a 10.3390/ph15030304 
500 |a 1424-8247 
520 |a 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 <b>9B</b> proved to be the most potent butyrylcholinesterase inhibitor (IC<sub>50</sub> = 2.93 µM) of the studied series. Computational studies were carried out to correlate the theoretical and experimental binding affinity of the compounds to the BChE protein. 
546 |a EN 
690 |a benzylbenzofuran 
690 |a butyrylcholinesterase inhibitors 
690 |a docking studies 
690 |a Medicine 
690 |a R 
690 |a Pharmacy and materia medica 
690 |a RS1-441 
655 7 |a article  |2 local 
786 0 |n Pharmaceuticals, Vol 15, Iss 3, p 304 (2022) 
787 0 |n https://www.mdpi.com/1424-8247/15/3/304 
787 0 |n https://doaj.org/toc/1424-8247 
856 4 1 |u https://doaj.org/article/3cefc231036d418d8eb266f5f45b3bf4  |z Connect to this object online.