Molecular docking studies of tea (Thea sinensis Linn.) polyphenols inhibition pattern with Rat P-glycoprotein

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Babar Ali ◽  
Qazi Mohammad Sajid Jamal ◽  
Showkat R. Mir ◽  
Saiba Shams ◽  
Mohammad Amjad Kamal
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Energy ◽  
Oral Administration ◽  
Docking Studies ◽  
Vital Role ◽  
Glycoprotein P ◽  
High Affinity ◽  
P Glycoprotein ◽  
Inhibition Pattern

AbstractSince 3000 B.C., evergreen plant Thea sinensis (Theaceae) is used both as a social and medicinal beverage. Leaves of T. sinensis contain amino acids, vitamins, caffeine, polysaccharides and polyphenols. Most of the natural medicinal actions of tea are due to the availability and abundance of polyphenols mainly catechins. It has also been stated that some catechins were absorbed more rapidly than other compounds after the oral administration of tea and could increase the bio-enhancing activities of anticancer drugs by inhibiting P-glycoprotein (P-gp). The results of the molecular docking showed that polyphenols bind easily to the active P-gp site. All compounds exhibited fluctuating binding affinity ranged from −11.67 to −8.36 kcal/mol. Observed binding energy required for theaflavin to bind to P-gp was lowest (−11.67 kcal/mol). The obtained data that supports all the selected polyphenols inhibited P-gp and therefore may enhance the bioavailability of drugs. This study may play a vital role in finding hotspots in P-gp and eventually may be proved useful in designing compounds with high affinity and specificity to the protein.

scholarly journals Molecular Docking and Dynamics Simulation Studies Predict Munc18b as a Target of Mycolactone: A Plausible Mechanism for Granule Exocytosis Impairment in Buruli Ulcer Pathogenesis

Toxins ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 181 ◽  
Author(s):  
Samuel Kwofie ◽  
Bismark Dankwa ◽  
Kweku Enninful ◽  
Courage Adobor ◽  
Emmanuel Broni ◽  
...  
Keyword(s):  
Wound Healing ◽  
Molecular Docking ◽  
Mast Cells ◽  
Binding Energy ◽  
Buruli Ulcer ◽  
Docking Studies ◽  
Dynamics Simulation ◽  
Granule Exocytosis ◽  
Molecular Docking Studies ◽  
Healing Processes

Ulcers due to infections with Mycobacterium ulcerans are characterized by complete lack of wound healing processes, painless, an underlying bed of host dead cells and undermined edges due to necrosis. Mycolactone, a macrolide produced by the mycobacterium, is believed to be the toxin responsible. Of interest and relevance is the knowledge that Buruli ulcer (BU) patients remember experiencing trauma previously at the site of the ulcers, suggesting an impairment of wound healing processes, the plausible effect due to the toxin. Wound healing processes involve activation of the blood platelets to release the contents of the dense granules mainly serotonin, calcium ions, and ADP/ATP by exocytosis into the bloodstream. The serotonin release results in attracting more platelets and mast cells to the wound site, with the mast cells also undergoing degranulation, releasing compounds into the bloodstream by exocytosis. Recent work has identified interference in the co-translational translocation of many secreted proteins via the endoplasmic reticulum and cell death involving Wiskott-Aldrich syndrome protein (WASP), Sec61, and angiotensin II receptors (AT2R). We hypothesized that mycolactone by being lipophilic, passively crosses cell membranes and binds to key proteins that are involved in exocytosis by platelets and mast cells, thus inhibiting the initiation of wound healing processes. Based on this, molecular docking studies were performed with mycolactone against key soluble n-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and regulators, namely Vesicle-associated membrane protein (VAMP8), Synaptosomal-associated protein (SNAP23, syntaxin 11, Munc13-4 (its isoform Munc13-1 was used), and Munc18b; and also against known mycolactone targets (Sec61, AT2R, and WASP). Munc18b was shown to be a plausible mycolactone target after the molecular docking studies with binding affinity of −8.5 kcal/mol. Structural studies and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding energy calculations of the mycolactone and Munc18b complex was done with 100 ns molecular dynamics simulations using GROMACS. Mycolactone binds strongly to Munc18b with an average binding energy of −247.571 ± 37.471 kJ/mol, and its presence elicits changes in the structural conformation of the protein. Analysis of the binding interactions also shows that mycolactone interacts with Arg405, which is an important residue of Munc18b, whose mutation could result in impaired granule exocytosis. These findings consolidate the possibility that Munc18b could be a target of mycolactone. The implication of the interaction can be experimentally evaluated to further understand its role in granule exocytosis impairment in Buruli ulcer.

scholarly journals Synthesis and Molecular Docking Studies of N,N-Dimethyl Arylpyranopyrimidinedione Derivatives

SynOpen ◽  
2022 ◽  
Vol 06 (01) ◽  
pp. 1-6
Author(s):  
Sivan Velmathi ◽  
Srinivasan Prabhakaran
Keyword(s):  
Molecular Docking ◽  
Reaction Mechanism ◽  
Binding Energy ◽  
Michael Addition ◽  
Barbituric Acid ◽  
Knoevenagel Condensation ◽  
Aromatic Aldehydes ◽  
Docking Studies ◽  
Reaction Sequence ◽  
Kinesin Eg5

AbstractThe synthesis of N,N-dimethyl arylpyranopyrimidinedione derivatives from aromatic aldehydes, N-methyl-1-(methylthio)-2-nitroethamine (NMSM) and 1,3-dimethyl barbituric acid, in the presence of piperidine as a catalyst, is reported. The reaction mechanism involves a Knoevenagel condensation, followed by Michael addition and intramolecular O-cyclization reaction sequence. The synthesized compounds were docked with human kinesin Eg5 protein to calculate binding energy, inhibition constant and H-bond interaction. All the compounds show good binding affinity towards the protein, with significant docking score.

scholarly journals Prediction of the Anxiolytic Action Mediated by the GABA A Receptor by the Molecular Docking Method

2020 ◽  
Vol 6 (5) ◽  
pp. 38-45
Author(s):  
T. Gendugov ◽  
A. Glushko ◽  
A. Chiriapkin ◽  
V. Chiriapkin
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Site ◽  
Computational Experiment ◽  
Gaba A ◽  
High Affinity ◽  
Docking Method ◽  
Benzodiazepine Binding ◽  
Docking Energy ◽  
Molecular Docking Method

The article considers the study in silico of the affinity of 3-[2-oxo-2-(4-phenyl-1-piperazinyl)ethyl]-4(3H)-quinazolinone (VMA-10-21 compound) to the benzodiazepine binding site of the GABA А receptor by molecular docking method. The computational experiment was carried out using a set of Autodock programs. As a result, the method for predicting the affinity of the simulated compounds to the benzodiazepine binding site of the GABA A receptor was developed. The highest correlation coefficient between the pKi value and the average docking energy in the benzodiazepine binding site (0.54) was obtained using a set of amino acids Tyr 58 and Tyr 159. The predicted Ki value of the VMA-10-21 compound is 2.864 nM, which suggests a high affinity of the studied compound to this receptor.

scholarly journals Antiviral potential of phytoligands against chymotrypsin-like protease of COVID‐19 virus using molecular docking studies: An optimistic approach

2020 ◽  
Author(s):  
Ratish Chandra Mishra ◽  
Rosy Kumari ◽  
Shivani Yadav ◽  
Jaya Parkash Yadav
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Drug Repositioning ◽  
Docking Studies ◽  
The Novel ◽  
Lead Compounds ◽  
Recent Outbreak ◽  
Novel Coronavirus ◽  
The City ◽  
Ucsf Chimera

Abstract A recent outbreak of the novel coronavirus, COVID‐19, in the city of Wuhan, Hubei province, China and its ensuing worldwide spread have resulted in lakhs of infections and thousands of deaths. As of now, there are no registered therapies for treating the contagious COVID‐19 infections, henceforth drug repositioning may provide a fast way out. In the present study, a total of thirty-five compounds including commonly used anti-viral drugs were screened against chymotrypsin-like protease (3CLpro) using SwissDock. Interaction between amino acid of targeted protein and ligands was visualized by UCSF Chimera. Docking studies revealed that the phytochemicals such as cordifolin, anisofolin A, apigenin 7-glucoside, luteolin, laballenic acid, quercetin, luteolin-4-glucoside exhibited significant binding energy with the enzyme viz. - 8.77, -8.72, -8.36, -8.35, -8.13, -8.04 and -7.87 Kcal/Mol respectively. Therefore, new lead compounds can be used for drug development against SARS‐CoV‐2 infections.

scholarly journals Напівемпіричний аналіз взаємодії алкоксипохідних 1,4-бенздіазепіну з ГАМКа-рецептором на підставі даних молекулярного докінгу та фармакологічного ефекту

2018 ◽  
Author(s):  
N. Ya. Golovenko ◽  
V. I. Pavlovskiy ◽  
I. P. Valivodz ◽  
V. B. Larionov
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Energy ◽  
Condensed System ◽  
Total Binding Energy ◽  
Ortho Position ◽  
Phenyl Radical ◽  
Benzodiazepine Derivatives ◽  
Effective Doses ◽  
Gaba Receptor Complex

Introduction. Pharmacological spectrum of 1.4-benzodiazepine 3-alkoxy derivatives, in contrast to classical substances, has more prominent analgesic properties, but even among the synthesized and studied molecules there are compounds with different magnitude of this effect.The aim of the study – to evaluate the molecular docking parameters of the theoretically generated structures of 1.4-benzodiazepine alkoxy derivatives with the GABA receptor complex and to compare these data with the pharmacological activity of the synthesized compounds.The molecular docking procedure was carried out using the iGEMDOCK v2.1 program, optimized structures of already synthesized and theoretically designed molecules with differing substituents in the ortho position of the phenyl radical and the "7" position of the condensed system are generated in the Avogadro program (v 1.2.0). The average effective doses of compounds (penthylenetetrazole-induced seizures, 120 mg/kg, subcutaneously 30 min after compounds administration) were studied in white mice.The binding energy of all the generated structures is within the ranges of 81.6–96.8 kcal/mol. Virtual docking data analysis of substituted alkoxy derivatives allows identifying several binding sites inherent for 7-chloro- or 7-bromo-substituted benzodiazepine derivatives. The greatest influence on the binding of chlorine-substituted alkoxy derivatives have regions with a high polarity amino acids (16-23 D) and similar hydrophilicity and hydrophobicity. The contribution of Van der Waals and hydrogen interactions to the total binding energy is determined by the presence of halogen (chlorine or bromine). In penthylenetetrazole-induced seizures test the compounds containing the chlorophenyl substituent in the hetero ring were most active (ED50 (0.42±0.10) μmol/kg for the propyloxy derivative and (0.51±0.17) μmol/kg for the ethyloxy derivative) while for the compounds with the phenyl radical, the ED50 value were much higher (5.1±2.7) μmol/kg and (17.75±1.93) μmol/kg, respectively). The analgesic effect is mainly due to the lkoxy derivatives possibility of binding to a center containing residues of basic amino acids.

scholarly journals PHYTOCHEMICAL TO INTERACT WITH NLS BINDING SITE ON IMA3 TO INHIBIT IMPORTIN Α/Β1 MEDIATED NUCLEAR IMPORT OF SARS-COV-2 CARGO

2020 ◽  
pp. 30-35
Author(s):  
BHARATH B. R. ◽  
HRISHIKESH DAMLE ◽  
SHIBAN GANJU ◽  
LATHA DAMLE
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Binding Site ◽  
Broad Spectrum ◽  
Nuclear Import ◽  
Docking Studies ◽  
Immunodeficiency Virus ◽  
Importin Α ◽  
Hiv 1 ◽  
Integrase Protein

Objective: Ivermectin is an FDA-approved, broad-spectrum anti-parasitic agent. It was originally identified as an inhibitor of interaction between the human 29 immunodeficiency virus-1 (HIV-1) integrase protein (IN) and the Importin (IMP) α/β1 30 heterodimers, which are responsible for IN nuclear import. Recent studies demonstrate that ivermectin is worthy of further consideration as a possible SARS-CoV-2 antiviral. Methods: We built the pathogen-host interactome and analyzed it using PHISTO. We compared Ivermectin and plant molecules for their interaction with Importin α3 (IMA3) using molecular docking studies. Results: A phytochemical ATRI001 with the lowest binding energy-7.290 Kcal/mol was found to be superior to Ivermectin with binding energy-4.946 Kcal/mol. Conclusion: ATRI001 may be a potential anti-SARS-CoV-2 agent; however, it requires clinical evaluation.

scholarly journals Involvement of P-glycoprotein and multidrug and toxin extrusion protein 1 in hepatic and renal berberine efflux in mice

RSC Advances ◽  
2017 ◽  
Vol 7 (55) ◽  
pp. 34801-34809 ◽  
Author(s):  
Guofeng Wang ◽  
Jingyi Jin ◽  
Jiakai Zeng ◽  
Rong Shi ◽  
Yan Dai ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Mouse Model ◽  
Glycoprotein P ◽  
Transfected Cells ◽  
P Glycoprotein ◽  
Toxin Extrusion

Involvement of P-glycoprotein (P-gp) and multidrug and toxin extrusion protein 1 (MATE1) in the hepatic and renal efflux of berberine was identified using transfected cells, a mouse model, and molecular docking.

Molecular Docking Studies on the Interaction of 2-Arylpropionate Esters with Candida rugosa Lipase

2014 ◽  
Vol 496-500 ◽  
pp. 520-523
Author(s):  
Xue Ying Liu ◽  
Hong Yan Zeng ◽  
Deng Hong Peng ◽  
Bi Foua Claude Alain Gohi ◽  
Qing Jun Huang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Molecular Mechanism ◽  
Asymmetric Catalysis ◽  
Candida Rugosa ◽  
Docking Studies ◽  
Enantioselective Hydrolysis ◽  
Molecular Docking Studies ◽  
Catalysis Mechanism

The interaction between ethyl 2-arylpropiolates and Candida rugosa lipase was studied by enantioselective hydrolysis and molecular docking. The ethyl 2-arylpropiolates with the lowest binding energy was selected to investigate the molecular mechanism of enzyme mediated asymmetric catalysis mechanism.

Sign in / Sign up

Export Citation Format

Share Document