scholarly journals Identification of Gly/NMDAR Antagonist from Chromolaena odorata’s Derived Phytoconstituents using Induced Fit Docking Approach

2019 ◽  
Author(s):  
Temitope Israel David ◽  
Olaposi Idowu. Omotuyi ◽  
Olalekan David Agboola ◽  
Dominic Chinedu Okonkwo ◽  
Niyi Samuel Adelakun
Keyword(s):  
Nmda Receptor ◽  
Ferulic Acid ◽  
Caffeic Acid ◽  
Binding Affinity ◽  
Receptor Site ◽  
Antagonistic Effect ◽  
Induced Fit Docking ◽  
Induced Fit ◽  
Docking Score ◽  
Docking Approach

AbstractThe ionotropic activation of N-methyl-D-aspartic acid (NMDA) plays a significant role in different type of neurodegenerative disease, as it is a tetramer with two Glycine binding subunit and two glutamate subunits. NMDA receptor can be inhibited by either blocking of the glycine site or glutamate site. Previously reported inhibitors of NMDA receptor focus on the inhibition of the glutamate subunit, which was reported to be associated with side effects such as ataxia, memory deficits, neurotoxicity. Therefore, different compounds with antagonistic effect are been explored on Gly/NMDA site. Glide XP docking was employed in screening phyto-constituent of Chromolaena odorata against Gly/NMDA receptor for hit compounds with antagonistic properties. The hit compounds were further subjected to Induced fit docking (IFD) and lipinski rule of five. The final selection was based on Rigid XP docking score using co-crystallized ligand as threshold docking score, interaction with receptor site residues, and IFD score. Ferulic acid, caffeic acid and scutellarein recorded binding affinity of −8.752Kcal/mol, 10.004 Kcal/mol and - 9.096 Kcal/mol respectively, which is higher than the binding affinity of co-crystallized ligand. Induced fit score obtained were −614.38, −614.03 and −616.31 for ferulic acid, caffeic acid and scutellarein respectively. The Adme properties of the phyto-constituent indicated that the compounds are drug-like in nature.

Induced-Fit Docking Approach Provides Insight into the Binding Mode and Mechanism of Action of HIV-1 Integrase Inhibitors

ChemMedChem ◽  
2009 ◽  
Vol 4 (9) ◽  
pp. 1446-1456 ◽  
Author(s):  
Maria Letizia Barreca ◽  
Nunzio Iraci ◽  
Laura De Luca ◽  
Alba Chimirri
Keyword(s):  
Mechanism Of Action ◽  
Binding Mode ◽  
Integrase Inhibitors ◽  
Induced Fit Docking ◽  
Induced Fit ◽  
Docking Approach ◽  
Insight Into ◽  
Hiv 1

scholarly journals Investigation of the Antioxidant Synergisms and Antagonisms among Caffeic, Ferulic and Rosmarinic Acids using the Briggs-Rauscher Reaction Method

2020 ◽  
Keyword(s):  
Antioxidant Activity ◽  
Ferulic Acid ◽  
Caffeic Acid ◽  
Phenolic Acids ◽  
Rosmarinic Acid ◽  
Antagonistic Effect ◽  
Individual Values ◽  
Potential Health ◽  
Reaction Method ◽  
Oscillating Reaction

Phenolic acids have been attracting huge attention over recent years due to their prominent antioxidant activity and potential health benefits. In this study, the antioxidant activity of caffeic, ferulic, and rosmarinic acids was evaluated using Briggs-Rauscher reaction method. In addition to single phenolic acids at different concentrations (50, 100, 200 and 250 µM), equimolar mixtures of two phenolic acids and all three phenolic acids were tested. The best ability to inhibit oscillations, i.e. the highest antioxidant activity showed rosmarinic acid at a concentration of 250 µM. Inhibition time of the Briggs-Rauscher oscillating reaction mixture was obtained experimentally for the different combinations of phenolic acids and compared with theoretical values calculated by adding up the effects of phenolic acids analyzed individually. The most of tested phenolic acids mixtures showed a difference in the antioxidant activity when compared to individual values of their constituents. The highest synergistic effect showed a mixture of caffeic acid and ferulic acid at a concentration of 250 µM while the highest antagonistic effect showed the mixture of caffeic acid, ferulic acid and rosmarinic acid at same concentration

scholarly journals Development of Putative Isospecific Inhibitors for HDAC6 using Random Forest, QM-Polarized docking, Induced-fit docking, and Quantum mechanics

2020 ◽  
Author(s):  
Ireoluwa Yinka Joel ◽  
Temidayo Olamide Adigun ◽  
Olukayode Olusola Bankole ◽  
Ahmeedah Ololade Ajibola ◽  
Emmanuel Bankole Ofeniforo ◽  
...  
Keyword(s):  
Quantum Mechanics ◽  
Random Forest ◽  
Binding Affinity ◽  
Active Site ◽  
Histone Deacetylases ◽  
Zinc Binding ◽  
Induced Fit Docking ◽  
Induced Fit ◽  
Reliable Model ◽  
High Binding Affinity

AbstractHistone deacetylases have been recognized as a potential target for epigenetic aberrance reversal in the various strategies for cancer therapy, with HDAC6 implicated in various forms of tumor growth and cancers. Diverse inhibitors of HDAC6 has been developed, however, there is still the challenge of iso-specificity and toxicity. In this study, we trained a Random forest model on all HDAC6 inhibitors curated in the ChEMBL database (3,742). Upon rigorous validations the model had an 85% balanced accuracy and was used to screen the SCUBIDOO database; 7785 hit compounds resulted and were docked into HDAC6 CD2 active-site. The top two compounds having a benzimidazole moiety as its zinc-binding group had a binding affinity of −78.56kcal/mol and −78.21kcal/mol respectively. The compounds were subjected to exhaustive docking protocols (Qm-polarized docking and Induced-Fit docking) in other to elucidate a binding hypothesis and accurate binding affinity. Upon optimization, the compounds showed improved binding affinity (−81.42kcal/mol), putative specificity for HDAC6, and good ADMET properties. We have therefore developed a reliable model to screen for HDAC6 inhibitors and suggested a series of benzimidazole based inhibitors showing high binding affinity and putative specificity for HDAC6.

Сrude Plant Extracts Mediated Polyphenol Oxidation Reactions in the Presence of 3-Methyl-2-Benzothiazolinone Hydrazone for the Determination of Total Polyphenol Content in Beverages

2018 ◽  
Vol 15 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Maria A. Morosanova ◽  
Anton S. Fedorov ◽  
Elena I. Morosanova
Keyword(s):  
Hydrogen Peroxide ◽  
Ferulic Acid ◽  
Gallic Acid ◽  
Caffeic Acid ◽  
Crude Extract ◽  
Reaction Rates ◽  
Green Bean ◽  
Polyphenol Content ◽  
Total Polyphenol ◽  
Total Polyphenol Content

Background: The consumption of antioxidants, including phenolic compounds, is considered important for preventing the oxidative damage diseases and ageing. The total polyphenol content (TPC) is the parameter used to estimate the quality of plant-derived products. Methods: Phenol oxidase activity of green bean (Phaseolus vulgaris) crude extract (in the presence of hydrogen peroxide) and banana (Musa sp.) pulp crude extract has been studied spectrophotometrically using catechol, gallic acid, caffeic acid, ferulic acid, and quercetin as substrates. All studied compounds have been oxidized in the presence of green bean crude extract and hydrogen peroxide; all studied compounds except ferulic acid have been oxidized in the presence of banana pulp crude extract. Michaelis constants (Km) and maximum reaction rates (Vmax) have been determined for oxidation in the presence of green bean crude extract and hydrogen peroxide (Km are 3.8×10-4 M, 1.6×10-3 M, 2.2×10-4 M, 2.3×10-4 M, 1.4×10-4 M and Vmax are 0.046 min-1, 0.102 min-1, 0.185 min-1, 0.053 min-1, 0.041 min-1 for catechol, gallic acid, caffeic acid, ferulic acid, and quercetin, respectively) and for oxidation in the presence of banana pulp crude extract (Km are 1.6×10-3 M, 3.8×10-3 M, 2.2×10-3 M, 4.2×10-4 M and Vmax are 0.058 min-1, 0.025 min-1, 0.027 min-1, 0.015 min-1 for catechol, gallic acid, caffeic acid, and quercetin, respectively). The influence of 3-methyl-2-benzothiazolinone hydrazone (MBTH) on the oxidation reactions kinetics has been studied: Michaelis constants values decrease and maximum reaction rates increase, which contributes to the increase in sensitivity of the determination. Results: Kinetic procedures of Total Polyphenol Content (TPC) determination using crude plants extracts in the presence of MBTH have been proposed (time of analysis is 1 min). For gallic acid (used as a standard for TPC determination) detection limit is 5.3×10-5 M, quantitation limit is 1.8×10-4 M, and linear range is 1.8×10-4 - 1.3×10-3 M for green bean crude extract; detection limit is 2.9×10-5 M, quantitation limit is 9.5×10-5 M, and linear range is 9.5×10-5 - 2.4×10-3 M for banana pulp crude extract. Proposed procedures are characterized by higher interference thresholds for sulfites, ascorbic acid, and citric acid compared to pure enzymes (horseradish peroxidase and mushroom tyrosinase) in the same conditions. Compared with standard Folin-Ciocalteu (FC) method the procedures described in this work are also characterized by less interference and more rapid determination. Conclusion: The procedures have been applied to TPC determination in tea, coffee, and wine samples. The results agree with the FC method for tea and coffee samples and are lower for wine samples, probably, due to sulfites interference.

Ferulic acid through mitigation of NMDA receptor pathway exerts anxiolytic-like effect in mouse model of maternal separation stress

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Zahra Lorigooini ◽  
Ali Nouri ◽  
Faezeh mottaghinia ◽  
Shima Balali-Dehkordi ◽  
Elham Bijad ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Mouse Model ◽  
Ferulic Acid ◽  
Nmda Receptors ◽  
Effective Dose ◽  
Life Stress ◽  
Receptor Agonist ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Central Zone

AbstractBackgroundExperiencing early-life stress plays an important role in the pathophysiology of anxiety disorders. Ferulic acid is a phenolic compound found in some plants which has several pharmacological properties. N-methyl-D-aspartate (NMDA) receptors are involved in the pathophysiology of mood disorders. In this study we aimed to assess the anxiolytic-like effect of ferulic acid in a mouse model of maternal separation (MS) stress by focusing on the possible involvement of NMDA receptors.MethodsMice were treated with ferulic acid (5 and 40 mg/kg) alone and in combination with NMDA receptor agonist/antagonist. Valid behavioral tests were performed, including open field test (OFT) and elevated plus maze test (EPM), while quantitative real time polymerase chain reaction (qRT-PCR) was used to evaluate gene expression of NMDA subunits (GluN2A and GluN2B) in the hippocampus.ResultsFindings showed that treatment of MS mice with ferulic acid increased the time spent in the central zone of the OFT and increased both open arm time and the percent of open arm entries in the EPM. Ferulic acid reduced the expression of NMDA receptor subunit genes. We showed that administration of NMDA receptor agonist (NMDA) and antagonist (ketamine) exerted anxiogenic and anxiolytic-like effects, correspondingly. Results showed that co-administration of a sub-effective dose of ferulic acid plus ketamine potentiated the anxiolytic-like effect of ferulic acid. Furthermore, co-administration of an effective dose of ferulic acid plus NMDA receptor agonist (NMDA) attenuated the anxiolytic-like effect of ferulic acid.ConclusionsIn deduction, our findings showed that NMDA, partially at least, is involved in the anxiolytic-like effect of ferulic acid in the OFT and EPM tests.

scholarly journals Molecular Docking and Molecular Dynamics Simulation Studies of Triterpenes from Vernonia patula with the Cannabinoid Type 1 Receptor

2021 ◽  
Vol 22 (7) ◽  
pp. 3595
Author(s):  
Md Afjalus Afjalus Siraj ◽  
Md. Sajjadur Rahman ◽  
Ghee T. Tan ◽  
Veronique Seidel
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Binding Affinity ◽  
Docking Studies ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Cannabinoid Type 1 Receptor ◽  
Docking Approach

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.

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