Profiling Auspicious Butyrylcholinesterase Inhibitory Activity of Two Herbal Molecules: Hyperforin and Hyuganin C

Cholinergic therapy based on cholinesterase (ChE) inhibitory drugs is the mainstay for the treatment of Alzheimer's disease. Therefore, an extensive research has been continuing for the discovery of drug candidates as inhibitors of acetyl‐ and butyrylcholinesterase. In this study, two natural m...

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Published inChemistry & biodiversity Vol. 16; no. 5; pp. e1900017 - n/a
Main Authors Orhan, Ilkay Erdogan, Senol Deniz, F. Sezer, Trædal‐Henden, Steinar, Cerón‐Carrasco, José P., den Haan, Helena, Peña‐García, Jorge, Pérez‐Sánchez, Horacio, Emerce, Esra, Skalicka‐Wozniak, Krystyna
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Published Switzerland Wiley Subscription Services, Inc 01.05.2019
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Abstract Cholinergic therapy based on cholinesterase (ChE) inhibitory drugs is the mainstay for the treatment of Alzheimer's disease. Therefore, an extensive research has been continuing for the discovery of drug candidates as inhibitors of acetyl‐ and butyrylcholinesterase. In this study, two natural molecules, e. g. hyperforin and hyuganin C were tested in vitro for their AChE and BChE inhibitory activity. Both of the compounds were ineffective against AChE, whereas hyperforin (IC50=141.60±3.39 μm) and hyuganin C (IC50=38.86±1.69 μm) were found to be the highly active inhibitors of BChE as compared to galantamine (IC50=46.58±0.91 μm) which was used as the reference. Then, these molecules were further proceeded to molecular docking experiments in order to establish their interactions at the active site of BChE. The molecular docking results indicated that both of them are able to block the access to key residues in the catalytic triad of the enzyme, while they complement some of the hydrophobic residues of the cavity, what is consistent with our in vitro data. While both compounds were predicted as mutagenic, only hyuganin C showed hepatotoxicity in in silico analysis. According to whole outcomes that we obtained, particularly hyuganin C besides hyperforin are the promising BChE inhibitors, which can be the promising compounds for AD therapy.
AbstractList Cholinergic therapy based on cholinesterase (ChE) inhibitory drugs is the mainstay for the treatment of Alzheimer's disease. Therefore, an extensive research has been continuing for the discovery of drug candidates as inhibitors of acetyl- and butyrylcholinesterase. In this study, two natural molecules, e. g. hyperforin and hyuganin C were tested in vitro for their AChE and BChE inhibitory activity. Both of the compounds were ineffective against AChE, whereas hyperforin (IC =141.60±3.39 μm) and hyuganin C (IC =38.86±1.69 μm) were found to be the highly active inhibitors of BChE as compared to galantamine (IC =46.58±0.91 μm) which was used as the reference. Then, these molecules were further proceeded to molecular docking experiments in order to establish their interactions at the active site of BChE. The molecular docking results indicated that both of them are able to block the access to key residues in the catalytic triad of the enzyme, while they complement some of the hydrophobic residues of the cavity, what is consistent with our in vitro data. While both compounds were predicted as mutagenic, only hyuganin C showed hepatotoxicity in in silico analysis. According to whole outcomes that we obtained, particularly hyuganin C besides hyperforin are the promising BChE inhibitors, which can be the promising compounds for AD therapy.
Cholinergic therapy based on cholinesterase (ChE) inhibitory drugs is the mainstay for the treatment of Alzheimer's disease. Therefore, an extensive research has been continuing for the discovery of drug candidates as inhibitors of acetyl- and butyrylcholinesterase. In this study, two natural molecules, e. g. hyperforin and hyuganin C were tested in vitro for their AChE and BChE inhibitory activity. Both of the compounds were ineffective against AChE, whereas hyperforin (IC50 =141.60±3.39 μm) and hyuganin C (IC50 =38.86±1.69 μm) were found to be the highly active inhibitors of BChE as compared to galantamine (IC50 =46.58±0.91 μm) which was used as the reference. Then, these molecules were further proceeded to molecular docking experiments in order to establish their interactions at the active site of BChE. The molecular docking results indicated that both of them are able to block the access to key residues in the catalytic triad of the enzyme, while they complement some of the hydrophobic residues of the cavity, what is consistent with our in vitro data. While both compounds were predicted as mutagenic, only hyuganin C showed hepatotoxicity in in silico analysis. According to whole outcomes that we obtained, particularly hyuganin C besides hyperforin are the promising BChE inhibitors, which can be the promising compounds for AD therapy.Cholinergic therapy based on cholinesterase (ChE) inhibitory drugs is the mainstay for the treatment of Alzheimer's disease. Therefore, an extensive research has been continuing for the discovery of drug candidates as inhibitors of acetyl- and butyrylcholinesterase. In this study, two natural molecules, e. g. hyperforin and hyuganin C were tested in vitro for their AChE and BChE inhibitory activity. Both of the compounds were ineffective against AChE, whereas hyperforin (IC50 =141.60±3.39 μm) and hyuganin C (IC50 =38.86±1.69 μm) were found to be the highly active inhibitors of BChE as compared to galantamine (IC50 =46.58±0.91 μm) which was used as the reference. Then, these molecules were further proceeded to molecular docking experiments in order to establish their interactions at the active site of BChE. The molecular docking results indicated that both of them are able to block the access to key residues in the catalytic triad of the enzyme, while they complement some of the hydrophobic residues of the cavity, what is consistent with our in vitro data. While both compounds were predicted as mutagenic, only hyuganin C showed hepatotoxicity in in silico analysis. According to whole outcomes that we obtained, particularly hyuganin C besides hyperforin are the promising BChE inhibitors, which can be the promising compounds for AD therapy.
Cholinergic therapy based on cholinesterase (ChE) inhibitory drugs is the mainstay for the treatment of Alzheimer's disease. Therefore, an extensive research has been continuing for the discovery of drug candidates as inhibitors of acetyl‐ and butyrylcholinesterase. In this study, two natural molecules, e. g. hyperforin and hyuganin C were tested in vitro for their AChE and BChE inhibitory activity. Both of the compounds were ineffective against AChE, whereas hyperforin (IC50=141.60±3.39 μm) and hyuganin C (IC50=38.86±1.69 μm) were found to be the highly active inhibitors of BChE as compared to galantamine (IC50=46.58±0.91 μm) which was used as the reference. Then, these molecules were further proceeded to molecular docking experiments in order to establish their interactions at the active site of BChE. The molecular docking results indicated that both of them are able to block the access to key residues in the catalytic triad of the enzyme, while they complement some of the hydrophobic residues of the cavity, what is consistent with our in vitro data. While both compounds were predicted as mutagenic, only hyuganin C showed hepatotoxicity in in silico analysis. According to whole outcomes that we obtained, particularly hyuganin C besides hyperforin are the promising BChE inhibitors, which can be the promising compounds for AD therapy.
Cholinergic therapy based on cholinesterase (ChE) inhibitory drugs is the mainstay for the treatment of Alzheimer's disease. Therefore, an extensive research has been continuing for the discovery of drug candidates as inhibitors of acetyl‐ and butyrylcholinesterase. In this study, two natural molecules, e. g. hyperforin and hyuganin C were tested in vitro for their AChE and BChE inhibitory activity. Both of the compounds were ineffective against AChE, whereas hyperforin (IC 50 =141.60±3.39 μ m ) and hyuganin C (IC 50 =38.86±1.69 μ m ) were found to be the highly active inhibitors of BChE as compared to galantamine (IC 50 =46.58±0.91 μ m ) which was used as the reference. Then, these molecules were further proceeded to molecular docking experiments in order to establish their interactions at the active site of BChE. The molecular docking results indicated that both of them are able to block the access to key residues in the catalytic triad of the enzyme, while they complement some of the hydrophobic residues of the cavity, what is consistent with our in vitro data. While both compounds were predicted as mutagenic, only hyuganin C showed hepatotoxicity in in silico analysis. According to whole outcomes that we obtained , particularly hyuganin C besides hyperforin are the promising BChE inhibitors, which can be the promising compounds for AD therapy.
Author den Haan, Helena
Pérez‐Sánchez, Horacio
Cerón‐Carrasco, José P.
Senol Deniz, F. Sezer
Orhan, Ilkay Erdogan
Peña‐García, Jorge
Skalicka‐Wozniak, Krystyna
Trædal‐Henden, Steinar
Emerce, Esra
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Keywords natural products
butyrylcholinesterase
molecular docking
enzyme inhibition
coumarin
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Snippet Cholinergic therapy based on cholinesterase (ChE) inhibitory drugs is the mainstay for the treatment of Alzheimer's disease. Therefore, an extensive research...
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StartPage e1900017
SubjectTerms Alzheimer's disease
butyrylcholinesterase
Catalysis
Cholinergics
Cholinesterase
coumarin
Drug development
enzyme inhibition
Galantamine
Hepatotoxicity
Hydrophobicity
Inhibitors
Molecular docking
natural products
Neurodegenerative diseases
Residues
Therapy
Title Profiling Auspicious Butyrylcholinesterase Inhibitory Activity of Two Herbal Molecules: Hyperforin and Hyuganin C
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fcbdv.201900017
https://www.ncbi.nlm.nih.gov/pubmed/30891904
https://www.proquest.com/docview/2226440624
https://www.proquest.com/docview/2194586793
Volume 16
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