Cholinesterase Enzymes Inhibitors from the Leaves of  Rauvolfia Reflexa and Their Molecular Docking Study

Fadaeinasab, Mehran; Hadi, A. Hamid A.; Kia, Yalda; Basiri, Alireza; Murugaiyah, Vikneswaran

doi:10.3390/molecules18043779

Cited by 25 publications

(18 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Acorenone B showed an inhibitory activity against AChE and BChE with IC 50 concentrations of 40.8 and 10.9 μg/mL, respectively ( Figure 4 ). These inhibitory potentials, even far from that of the reference compound donepezil (6.7 nM) versus AChE [ 38 ], are close to those previously published for galanthamine (2.2 µg/mL and 11.7 µg/mL) or other plant extracts [ 4 , 39 , 40 ]. Interestingly, in spite of its moderate inhibitory potential, galanthamine is a typical drug used for the treatment of Alzheimer's disease [ 41 ], validating our efforts to identify new potential inhibitory compounds.…”

Section: Resultssupporting

confidence: 85%

“…Plants are rich in structurally diverse secondary metabolites displaying a wide range of biological activities, including possible leads for the treatment of neurodegenerative diseases [ 2 , 3 ]. Natural products have contributed greatly as sources for drug discovery for Alzheimer’s disease [ 4 ]. Earlier studies have shown that the maintenance of correct levels of acetylcholinesterases is directly related to different diseases such as Alzheimer's disease (AD), bipolar disorder, depression, and schizophrenia [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Acorenone B: AChE and BChE Inhibitor as a Major Compound of the Essential Oil Distilled from the Ecuadorian Species Niphogeton dissecta (Benth.) J.F. Macbr

et al. 2017

View full text Add to dashboard Cite

This study investigated the chemical composition, physical proprieties, biological activity, and enantiomeric analysis of the essential oil from the aerial parts of Niphogeton dissecta (culantrillo del cerro) from Ecuador, obtained by steam distillation. The qualitative and quantitative analysis of the essential oil was realized by gas chromatographic and spectroscopic techniques (GC-MS and GC-FID). Acorenone B was identified by GC-MS and NMR experiments. The enantiomeric distribution of some constituents has been assessed by enantio-GC through the use of a chiral cyclodextrin-based capillary column. We identified 41 components that accounted for 96.46% of the total analyzed, the major components were acorenone B (41.01%) and (E)-β-ocimene (29.64%). The enantiomeric ratio of (+)/(−)-β-pinene was 86.9:13.1, while the one of (+)/(−)-sabinene was 80.9:19.1. The essential oil showed a weak inhibitory activity, expressed as Minimal Inhibitory Concentration (MIC), against Enterococcus faecalis (MIC 10 mg/mL) and Staphylococcus aureus (MIC 5 mg/mL). Furthermore, it inhibited butyrylcholinesterase with an IC50 value of 11.5 μg/mL. Pure acorenone B showed inhibitory activity against both acetylcholinesterase and butyrylcholinesterase, with IC50 values of 40.8 μg/mL and 10.9 μg/mL, respectively.

show abstract

Section: Resultssupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Acorenone B: AChE and BChE Inhibitor as a Major Compound of the Essential Oil Distilled from the Ecuadorian Species Niphogeton dissecta (Benth.) J.F. Macbr

et al. 2017

View full text Add to dashboard Cite

show abstract

“…As mentioned before, different challenges arise during the treatment of OPs intoxications with oxime‐based drugs. One relies in the repetitive evaluation of oxime modifications to reactivate AChEs, instead of looking for new scaffolds as potential pharmacophores . For example, structure‐activity relationships (SAR) studies have reported the synthesis of 134 novel oxime‐based molecules, primarily imidazole aldoximes and hydroxymino acetamide derivatives .…”

Section: Resultsmentioning

confidence: 99%

“…One relies in the repetitive evaluation of oxime modifications to reactivate AChEs, instead of looking for new scaffolds as potential pharmacophores. [52][53][54][55] For example, structure-activity relationships (SAR) studies have reported the synthesis of 134 novel oxime-based molecules, primarily imidazole aldoximes and hydroxymino acetamide derivatives. [56] Most of them showed reasonable reactivation rates associated to ionization states that confer higher nucleophilic reactivity to the oxime group.…”

Section: Perspectives Of Novel Scaffolds As Ache Reactivatorsmentioning

confidence: 99%

Prediction of Ligands Binding Acetylcholinesterase with Potential Antidotal Activity: A Virtual Screening Approach

Ochoa

Rodríguez

Zuluaga

2019

Molecular Informatics

View full text Add to dashboard Cite

Intoxications caused by organophosphorus compounds (OPs) are associated with the reversible, and sometimes irreversible interaction with acetylcholinesterase (AChE). OPs are commonly used as pesticides mainly in developing countries, where the associated poisoning is a major health problem related to suicidal attempts, careless manipulation, and chemical warfare. The current antidotes are oxime‐based drugs that can regenerate the AChE catalytic activity. Nevertheless, challenges associated with lack of efficiency and difficulties for crossing blood‐brain barrier have motivated the design of novel alternatives. We used a validated molecular docking approach for the virtual screening of 579,890 synthetic ligands and 478 drugs against a human AChE in its apo conformation, and a murine AChE conjugated with the OP tabun. After filtering, 7 hits were selected as potential competitors due to the formation of key interactions within the active site gorge of the AChE structure, and potential reactivators based on interactions with amino acids of the catalytic triad in the presence of organophosphorus compounds. The selected candidates will be further evaluated through in vitro and in vivo assays.

show abstract

“…All two-dimensional images of ligand-protein interactions were generated using LIGPLOT version 4.5.3. [ 9 ]…”

Section: Methodsmentioning

confidence: 99%

In vitro acetylcholinesterase inhibition by psoralen using molecular docking and enzymatic studies

Somani¹,

Kulkarni²,

Shinde³

et al. 2015

J Pharm Bioall Sci

View full text Add to dashboard Cite

Introduction:Alzheimer's disease (AD) has increased at an alarming rate and is now a worldwide health problem. Inhibitors of acetylcholinesterase (AChE) leading to inhibition of acetylcholine breakdown constitute the main therapeutic strategy for AD. Psoralen was investigated as inhibitor of AChE enzyme in an attempt to explore its potential for the management of AD.Materials and Methods:Psoralen was isolated from powdered Psoralea corylifolia fruits. AChE enzyme inhibitory activity of different concentrations of psoralen was investigated by use of in vitro enzymatic and molecular docking studies. Further, the enzyme kinetics were studied using Lineweaver-Burk plot.Results:Psoralen was found to inhibit AChE enzyme activity in a concentration-dependent manner. Kinetic studies showed psoralen inhibits AChE in a competitive manner. Molecular docking study revealed that psoralen binds well within the binding site of the enzyme showing interactions such as π-π stacking and hydrogen bonding with residues present therein.Conclusion:The result of AChE enzyme inhibitory activity of the psoralen in this study is promising. It could be further explored as a potential candidate for further development of new drugs against AD.

show abstract

Cholinesterase Enzymes Inhibitors from the Leaves of Rauvolfia Reflexa and Their Molecular Docking Study

Cited by 25 publications

References 15 publications

Acorenone B: AChE and BChE Inhibitor as a Major Compound of the Essential Oil Distilled from the Ecuadorian Species Niphogeton dissecta (Benth.) J.F. Macbr

Acorenone B: AChE and BChE Inhibitor as a Major Compound of the Essential Oil Distilled from the Ecuadorian Species Niphogeton dissecta (Benth.) J.F. Macbr

Prediction of Ligands Binding Acetylcholinesterase with Potential Antidotal Activity: A Virtual Screening Approach

In vitro acetylcholinesterase inhibition by psoralen using molecular docking and enzymatic studies

Contact Info

Product

Resources

About