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-(<i>p</i>-tolylsulfonamido)benzamide derivatives. These 5-styrylbenzamide derivatives were evaluated through enzymatic assays in vitro for their capability to inhibit acetylcholinesterase (AChE), butyrylchol...
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MDPI AG
2021-04-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/5/647 |
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doaj-3fcd856218fe4a9287f4ee501cfdf0d72021-04-22T23:06:21ZengMDPI AGAntioxidants2076-39212021-04-011064764710.3390/antiox10050647In 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 PropertiesMalose J. Mphahlele0Emmanuel N. Agbo1Garland K. More2Samantha Gildenhuys3Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South AfricaDepartment of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South AfricaDepartment of Life & Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South AfricaDepartment of Life & Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South AfricaThe 5-(styryl)anthranilamides were transformed into the corresponding 5-styryl-2-(<i>p</i>-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 <b>2a </b>and <b>3b </b>have the capability of scavenging free radicals. The potential of the most active compound, 5-styrylbenzamide (<b>2a</b>), 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.https://www.mdpi.com/2076-3921/10/5/6475-Styrylbenzamidescholinesteraseβ-secretaseantioxidantmetal chelatingdrug-receptor interactions |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Malose J. Mphahlele Emmanuel N. Agbo Garland K. More Samantha Gildenhuys |
| spellingShingle |
Malose J. Mphahlele Emmanuel N. Agbo Garland K. More Samantha Gildenhuys 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 Antioxidants 5-Styrylbenzamides cholinesterase β-secretase antioxidant metal chelating drug-receptor interactions |
| author_facet |
Malose J. Mphahlele Emmanuel N. Agbo Garland K. More Samantha Gildenhuys |
| author_sort |
Malose J. Mphahlele |
| 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_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_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_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 |
| publisher |
MDPI AG |
| series |
Antioxidants |
| issn |
2076-3921 |
| publishDate |
2021-04-01 |
| description |
The 5-(styryl)anthranilamides were transformed into the corresponding 5-styryl-2-(<i>p</i>-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 <b>2a </b>and <b>3b </b>have the capability of scavenging free radicals. The potential of the most active compound, 5-styrylbenzamide (<b>2a</b>), 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. |
| topic |
5-Styrylbenzamides cholinesterase β-secretase antioxidant metal chelating drug-receptor interactions |
| url |
https://www.mdpi.com/2076-3921/10/5/647 |
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