Exploration of the Acetylcholinesterase Inhibitory Activity of Some Alkaloids from Amaryllidaceae Family by Molecular Docking In Silico

Background: Postprandial hyperglycemia can be reduced by inhibiting major carbohydrate hydrolyzing enzymes, such as α-glucosidase and α-amylase which is an effective approach in both preventing and treating diabetes. Objective: The aim of this study was to synthesize a series of 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl] benzoic acid derivatives and evaluate α-glucosidase and α-amylase inhibitory activity along with molecular docking and in silico ADMET property analysis. Method: Chlorosulfonation of 2,4-dichloro benzoic acid followed by reaction with corresponding anilines/amines yielded 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic acid derivatives. For evaluating their antidiabetic potential α-glucosidase and α-amylase inhibitory assays were carried out. In silico molecular docking studies of these compounds were performed with respect to these enzymes and a computational study was also carried out to predict the drug-likeness and ADMET properties of the title compounds. Results: Compound 3c (2,4-dichloro-5-[(2-nitrophenyl)sulfamoyl]benzoic acid) was found to be highly active having 3 fold inhibitory potential against α-amylase and 5 times inhibitory activity against α-glucosidase in comparison to standard drug acarbose. Conclusion: Most of the synthesized compounds were highly potent or equipotent to standard drug acarbose for inhibitory potential against α-glucosidase and α-amylase enzyme and hence this may indicate their antidiabetic activity. The docking study revealed that these compounds interact with active site of enzyme through hydrogen bonding and different pi interactions.

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In vitro cytotoxicity assay, mushroom tyrosinase inhibitory activity and release analysis of kojic monooleate nanodelivery system and In silico molecular docking study against 2Y9X target enzyme

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2021.102764 ◽

2021 ◽

pp. 102764

Author(s):

Muhammad Azimuddin Roselan ◽

Norzalina Zakaria ◽

Nur Hana Faujan ◽

Muhammad Alif Mohammad Latif ◽

Siti Munirah Mohd Faudzi ◽

...

Keyword(s):

Molecular Docking ◽

Inhibitory Activity ◽

In Silico ◽

Docking Study ◽

In Vitro Cytotoxicity ◽

Mushroom Tyrosinase ◽

Molecular Docking Study ◽

Release Analysis ◽

In Silico Molecular Docking

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Bioactive constituents from roots of Salvia syriaca L.: Acetylcholinesterase inhibitory activity and molecular docking studies

South African Journal of Botany ◽

10.1016/j.sajb.2015.12.003 ◽

2016 ◽

Vol 106 ◽

pp. 1-4 ◽

Cited By ~ 26

Author(s):

Mir Babak Bahadori ◽

Leila Dinparast ◽

Hassan Valizadeh ◽

Mahdi Moridi Farimani ◽

Samad Nejad Ebrahimi

Keyword(s):

Molecular Docking ◽

Inhibitory Activity ◽

Docking Studies ◽

Bioactive Constituents ◽

Molecular Docking Studies ◽

Acetylcholinesterase Inhibitory Activity

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Chemical Profile, Antioxidant and Alpha-Amylase Inhibitory Activity of Leaves Extracts of Annona muricata: A Combined In vitro and In silico Study

Letters in Applied NanoBioScience ◽

10.33263/lianbs112.34703479 ◽

2021 ◽

Vol 11 (2) ◽

pp. 3470-3479

Keyword(s):

Molecular Docking ◽

Inhibitory Activity ◽

In Silico ◽

Molecular Mechanisms ◽

Hydrophobic Interactions ◽

In Silico Analysis ◽

Gas Chromatography Mass Spectrometry ◽

Annona Muricata ◽

Butanol Extract

Leaves of Annona muricata are commonly used for treating diabetes. This study was conducted to investigate the molecular mechanisms involved in the antidiabetic properties of leaves of Annona muricata. Leaves of Annona muricata were extracted separately with H2O, hydromethanol (50% methanol), methanol, ethylacetate, and n-butanol. Chemical characterization of the extracts was performed by spectrophotometry and Gas chromatography-Mass Spectrometry (GC-MS) techniques. Biological activity was determined by α-amylase inhibition assays and molecular docking. The hydromethanol extract had a total phenolics concentration of 117.00±0.59 µg GAE/mg extract whereas; flavonoids were most abundant in the n-butanol extract accounting for 29.34±8.87 µg QE/mg extract. The n-butanol extract had the best FRAP value of 41.17±0.57 Vit C eqv mM, which was significantly higher than the value of the vitamin C reference. Estimated IC50 for all the extracts did not differ significantly but was significantly higher than the reference compound quercetin. All extracts inhibited α-amylase in vitro albeit significantly lower than acarbose. The hydromethanol extract had the highest inhibitory activity (53.31 ± 0.33%). Furthermore, chemical profiling of the hydromethanol extract revealed the presence of a variety of bioactive compounds. In silico analysis by molecular docking of the compounds identified by GC-MS on α-amylase revealed that the compounds had robust molecular interactions orchestrated by H-bonding and hydrophobic interactions. From the results, it can be concluded that extracts of Annona muricata possess antioxidant phytochemicals that inhibit α-amylase. Therefore, the results justify the use of the plant for the treatment of diabetes.

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Euryops pectinatus L. Flower Extract Inhibits P-glycoprotein and Reverses Multi-Drug Resistance in Cancer Cells: A Mechanistic Study

Molecules ◽

10.3390/molecules25030647 ◽

2020 ◽

Vol 25 (3) ◽

pp. 647 ◽

Cited By ~ 1

Author(s):

Wafaa M. Elkady ◽

Iriny M. Ayoub ◽

Yousra Abdel-Mottaleb ◽

Mohamed F. ElShafie ◽

Michael Wink

Keyword(s):

Molecular Docking ◽

Multidrug Resistance ◽

Cancer Cells ◽

Inhibitory Activity ◽

In Silico ◽

Chemotherapeutic Agents ◽

Selective Cytotoxicity ◽

Flower Extract ◽

P Glycoprotein ◽

In Silico Molecular Docking

Euryops pectinatus is a South African ornamental plant belonging to family Asteraceae. The present work evaluates the cytotoxic activity and phytochemical profile of the flower extract. Metabolite profiling was performed using HPLC-PDA-ESI-MS/MS. Total phenolics and flavonoids content were assessed. Cytotoxicity was evaluated against 6 different cancer cell lines using MTT assay. The possible underlying mechanism was proposed. We analyzed whether the extract could overcome the resistance of multidrug-resistant cancer cells for doxorubicin. The effect of combination of E. pectinatus with doxorubicin was also studied. Additionally, the potential inhibitory activity of the identified phytochemicals to PB1 protein was analyzed using in silico molecular docking. Twenty-five compounds were tentatively identified. Total phenolic and flavonoid contents represented 49.41 ± 0.66 and 23.37 ± 0.23 µg/mg dried flower extract, respectively. The extract showed selective cytotoxicity against Caco2 cells but its main effect goes beyond mere cytotoxicity. It showed strong inhibition of P-glycoprotein, which helps to overcome multidrug resistance to classical chemotherapeutic agents. In silico molecular docking showed that dicaffeoyl quinic acid, kaempferol-O-rutinoside, rutin, and isorhamnetin-O-rutinoside exhibited the most potent inhibitory activity to PB1 involved in tumor progression. Euryops pectinatus flower heads could have promising selective cytotoxicity alone or in combination with other chemotherapeutic agents to counteract multidrug resistance.

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De-novo Drug Design, Molecular Docking and In-Silico Molecular Prediction of AChEI Analogues through CADD Approaches as Anti-Alzheimer’s Agents

Current Computer - Aided Drug Design ◽

10.2174/1573409915666190301124210 ◽

2020 ◽

Vol 16 (1) ◽

pp. 54-72 ◽

Cited By ~ 2

Author(s):

Surabhi Pandey ◽

B.K. Singh

Keyword(s):

Molecular Docking ◽

Drug Design ◽

Inhibitory Activity ◽

In Silico ◽

Active Sites ◽

De Novo ◽

Docking Studies ◽

Target Protein ◽

Design And Development ◽

Reference Drug

Background: There are over 44 million persons who suffer with Alzheimer’s disease (AD) worldwide, no existence of cure and only symptomatic treatments are available for it. The aim of this study is to evaluate the anti-Alzheimer potential of designed AChEI analogues using computer simulation docking studies. AChEIs are the most potential standards for treatment of AD, because they have proven efficacy. Among all AChEIs donepezil possesses lowest adverse effects, it can treat mildmoderate- severe AD and only once-daily dosing is required. Therefore, donepezil is recognized as a significant prototype for design and development of new drug molecule. Methods: In this study the Inhibitory potential of the design compounds on acetylcholinesterase enzyme has been evaluated. Docking studies has been performed which further analyzed by in-silico pharmacokinetic evaluation through pharmacopredicta after that Interaction modes with enzyme active sites were determined. Docking studies revealed that there is a strong interaction between the active sites of AChE enzyme and analyzed compounds. Results: As a result 26 compounds have been indicates better inhibitory activity on AChE enzyme and all the screening parameters have also been satisfied by all 26 compounds. From these 26 compounds, six compounds 17, 18, 24, 30, 36 and 56 are found to be the most potent inhibitors of this series by insilico study through INVENTUS v 1.1 software, having highest bio-affinities i.e. - 8.51, - 7.67, - 8.30, - 7.59, - 8.71 and -7.62 kcal/mol respectively, while the standard or reference drug donepezil had binding affinity of - 6.32 kcal/mol. Conclusion: Computer aided drug design approach has been playing an important role in the design and development of novel anti- AD drugs. With the help of structure based drug design some novel analogues of donepezil have been designed and the molecular docking studies with structure based ADME properties prediction studies is performed for prediction of AChE inhibitory activity. The binding mode of proposed compounds with target protein i.e. AChE has been evaluated and the resulting data from docking studies explains that all of the newly designed analogues had significantly high affinity towards target protein compared to donepezil as a reference ligand.

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