Cargando…

In Vitro Enzymatic and Kinetic Studies, and In Silico Drug-Receptor Interactions, and Drug-Like Profiling of the 5-Styrylbenzamide Derivatives as Potential Cholinesterase and β-Secretase Inhibitors with Antioxidant Properties

The 5-(styryl)anthranilamides were transformed into the corresponding 5-styryl-2-(p-tolylsulfonamido)benzamide derivatives. These 5-styrylbenzamide derivatives were evaluated through enzymatic assays in vitro for their capability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE),...

Descripción completa

Detalles Bibliográficos
Autores principales: Mphahlele, Malose J., Agbo, Emmanuel N., More, Garland K., Gildenhuys, Samantha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145986/
https://www.ncbi.nlm.nih.gov/pubmed/33922328
http://dx.doi.org/10.3390/antiox10050647
_version_ 1783697295350431744
author Mphahlele, Malose J.
Agbo, Emmanuel N.
More, Garland K.
Gildenhuys, Samantha
author_facet Mphahlele, Malose J.
Agbo, Emmanuel N.
More, Garland K.
Gildenhuys, Samantha
author_sort Mphahlele, Malose J.
collection PubMed
description The 5-(styryl)anthranilamides were transformed into the corresponding 5-styryl-2-(p-tolylsulfonamido)benzamide derivatives. These 5-styrylbenzamide derivatives were evaluated through enzymatic assays in vitro for their capability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) activities as well as for antioxidant potential. An in vitro cell-based antioxidant activity assay involving lipopolysaccharides (LPS)-induced reactive oxygen species (ROS) production revealed that compounds 2a and 3b have the capability of scavenging free radicals. The potential of the most active compound, 5-styrylbenzamide (2a), to bind copper (II) or zinc (II) ions has also been evaluated spectrophotometrically. Kinetic studies of the most active derivatives from each series against the AChE, BChE, and β-secretase activities have been performed. The experimental results are complemented with molecular docking studies into the active sites of these enzymes to predict the hypothetical protein–ligand binding modes. Their drug likeness properties have also been predicted.
format Online
Article
Text
id pubmed-8145986
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-81459862021-05-26 In Vitro Enzymatic and Kinetic Studies, and In Silico Drug-Receptor Interactions, and Drug-Like Profiling of the 5-Styrylbenzamide Derivatives as Potential Cholinesterase and β-Secretase Inhibitors with Antioxidant Properties Mphahlele, Malose J. Agbo, Emmanuel N. More, Garland K. Gildenhuys, Samantha Antioxidants (Basel) Article The 5-(styryl)anthranilamides were transformed into the corresponding 5-styryl-2-(p-tolylsulfonamido)benzamide derivatives. These 5-styrylbenzamide derivatives were evaluated through enzymatic assays in vitro for their capability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) activities as well as for antioxidant potential. An in vitro cell-based antioxidant activity assay involving lipopolysaccharides (LPS)-induced reactive oxygen species (ROS) production revealed that compounds 2a and 3b have the capability of scavenging free radicals. The potential of the most active compound, 5-styrylbenzamide (2a), to bind copper (II) or zinc (II) ions has also been evaluated spectrophotometrically. Kinetic studies of the most active derivatives from each series against the AChE, BChE, and β-secretase activities have been performed. The experimental results are complemented with molecular docking studies into the active sites of these enzymes to predict the hypothetical protein–ligand binding modes. Their drug likeness properties have also been predicted. MDPI 2021-04-22 /pmc/articles/PMC8145986/ /pubmed/33922328 http://dx.doi.org/10.3390/antiox10050647 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mphahlele, Malose J.
Agbo, Emmanuel N.
More, Garland K.
Gildenhuys, Samantha
In Vitro Enzymatic and Kinetic Studies, and In Silico Drug-Receptor Interactions, and Drug-Like Profiling of the 5-Styrylbenzamide Derivatives as Potential Cholinesterase and β-Secretase Inhibitors with Antioxidant Properties
title In Vitro Enzymatic and Kinetic Studies, and In Silico Drug-Receptor Interactions, and Drug-Like Profiling of the 5-Styrylbenzamide Derivatives as Potential Cholinesterase and β-Secretase Inhibitors with Antioxidant Properties
title_full In Vitro Enzymatic and Kinetic Studies, and In Silico Drug-Receptor Interactions, and Drug-Like Profiling of the 5-Styrylbenzamide Derivatives as Potential Cholinesterase and β-Secretase Inhibitors with Antioxidant Properties
title_fullStr In Vitro Enzymatic and Kinetic Studies, and In Silico Drug-Receptor Interactions, and Drug-Like Profiling of the 5-Styrylbenzamide Derivatives as Potential Cholinesterase and β-Secretase Inhibitors with Antioxidant Properties
title_full_unstemmed In Vitro Enzymatic and Kinetic Studies, and In Silico Drug-Receptor Interactions, and Drug-Like Profiling of the 5-Styrylbenzamide Derivatives as Potential Cholinesterase and β-Secretase Inhibitors with Antioxidant Properties
title_short In Vitro Enzymatic and Kinetic Studies, and In Silico Drug-Receptor Interactions, and Drug-Like Profiling of the 5-Styrylbenzamide Derivatives as Potential Cholinesterase and β-Secretase Inhibitors with Antioxidant Properties
title_sort in vitro enzymatic and kinetic studies, and in silico drug-receptor interactions, and drug-like profiling of the 5-styrylbenzamide derivatives as potential cholinesterase and β-secretase inhibitors with antioxidant properties
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145986/
https://www.ncbi.nlm.nih.gov/pubmed/33922328
http://dx.doi.org/10.3390/antiox10050647
work_keys_str_mv AT mphahlelemalosej invitroenzymaticandkineticstudiesandinsilicodrugreceptorinteractionsanddruglikeprofilingofthe5styrylbenzamidederivativesaspotentialcholinesteraseandbsecretaseinhibitorswithantioxidantproperties
AT agboemmanueln invitroenzymaticandkineticstudiesandinsilicodrugreceptorinteractionsanddruglikeprofilingofthe5styrylbenzamidederivativesaspotentialcholinesteraseandbsecretaseinhibitorswithantioxidantproperties
AT moregarlandk invitroenzymaticandkineticstudiesandinsilicodrugreceptorinteractionsanddruglikeprofilingofthe5styrylbenzamidederivativesaspotentialcholinesteraseandbsecretaseinhibitorswithantioxidantproperties
AT gildenhuyssamantha invitroenzymaticandkineticstudiesandinsilicodrugreceptorinteractionsanddruglikeprofilingofthe5styrylbenzamidederivativesaspotentialcholinesteraseandbsecretaseinhibitorswithantioxidantproperties