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...
Saved in:
Main Authors: | , , , , , , |
---|---|
Format: | Book |
Published: |
MDPI AG,
2022-03-01T00:00:00Z.
|
Subjects: | |
Online Access: | Connect to this object online. |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
MARC
LEADER | 00000 am a22000003u 4500 | ||
---|---|---|---|
001 | doaj_3cefc231036d418d8eb266f5f45b3bf4 | ||
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. |