scholarly journals Molecular Docking studies of Phytocompounds of Rheum emodi Wall with proteins responsible for antibiotic resistance in bacterial and fungal pathogens: In silico approach to enhance the bio-availability of antibiotics

2020 ◽  
Author(s):  
Rajan Rolta ◽  
Vikas Kumar ◽  
Anuradha Sourirajan ◽  
Kamal Dev
Keyword(s):  
Antibiotic Resistance ◽  
Binding Energy ◽  
Fungal Pathogens ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Penicillin Binding Protein ◽  
Toxicity Prediction ◽  
Pharmacological Activities

AbstractRheum emodi Wall. (Himalayan rhubarb) has been used to cure many human diseases. Literature survey demonstrated that it has many pharmacological activities such as antioxidant, antimicrobial, antiviral, anticancer and wound healing. The present study was aimed to understand if major phytocompounds of Rheum emodi could bind proteins responsible for antibiotic resistance in bacterial and fungal pathogens and enhance the potency of antibiotics. The major phytocompounds of R. emodi (emodin, rhein-13c6 and chrysophenodimethy ether) were retrieved from Pubchem and target proteins were retrieved from RCSB protein data bank. The docking study was performed with Hex 8.0.0 software and molinspiration, swiss ADME servers were used for determination of Lipinski rule of 5, drug-likeness prediction respectively, whereas, admetSAR and Protox-II tools were used for toxicity prediction. Among all the selected phytocompounds, emodin showed the best binding energy of −235.82 Kcal mol-1 and −245 Kcal mol-1 with cytochrome P450 14 alpha-sterol demethylase (PDB ID: 1EA1) and N-myristoyl transferase (PDB ID: 1IYL) receptors, respectively, which is more than that of fluconazole (−224.12 kcalmol-1 and −161.14 kcal mol-1). Similarly, with Penicillin binding protein 3 (PDB ID: 3VSL) receptor, emodin and Chrysophanol dimethyl ether showed highest binding energy of - 216.68 Kcal mol-1 and −215.58 kcal mol-1 which is comparable to erythromycin (−263.63 kcal mol-1), chloramphanicol (−217.34 kcal mol-1) and tetracycline (−263.63 kcal mol-1). All the selected phytocompounds also fulfill Lipinski rule, non-carcinogenic and non-cytotoxic in nature. These compounds also showed high LD50 value showing non-toxicity of these phytocompounds.Graphical abstract

scholarly journals SOLATION, CHARACTERIZATION, AND DOCKING STUDIES OF ISOLATED COMPOUNDS AS ANTIDIABETIC MOLECULES FROM CRESSA CRETICA

2020 ◽  
pp. 84-91
Author(s):  
SANGEETA RANI ◽  
KAVITA GAHLOT ◽  
ARVIND KUMAR
Keyword(s):  
Molecular Docking ◽  
Spectroscopic Analysis ◽  
Three Dimensional ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Dimensional Structure ◽  
Lead Target ◽  
Coarse Powder ◽  
Autodock 4.0

Objective: The purpose of this study was to investigate the diabetic effect of phytocompounds isolated from Cressa cretica Linn. using spectroscopic analysis and molecular docking studies. Methods: Coarse powder of the whole plant of C. cretica was extracted with methanol, extracted part was subjected to silica column isolation, and two compounds: 2-Isopropyl-4-(1-methyl-dodeca-2,4-dienyloxy)-benzene-1,3,5-triol (Compound CN-01) and 11-Methyl-dodeca-2,4,6,8,10-pentenoic acid 2,3-dihydroxy-5-methyl-phenyl ester (Compound CN-02) were isolated in pure form. The three-dimensional structure of target protein was downloaded from PDB (www.rcsb.org) Protein Data Bank, Ligand file CN – 01 and CN – 02 were converted to MDL Molfile (V2000) format using ChemSketch 2017.2.1. These files could not be used directly in AutoDock 4.0 tools; thus, they were first converted to PDB files using an open babel tool. Results: Compounds were revealed through spectroscopic analysis and screened using AutoDock 4.0 tools. Docking study recommended that CN – 01 and CN – 02 an existing phytochemical from the plant of C. cretica had the highest fitness docking score and hence could be a potent antidiabetic drug. Conclusion: In this investigation, we docked the receptor (glycogen phosphorylase protein) holds a promising lead target formation against diabetes based on molecular docking analysis (minimum hydrogen bond length and maximum docked score). Thus, these compounds can be effectively used as drugs for treating diabetes which is predicted on the basis of docking scores.

scholarly journals A Molecular Docking Study of N-Ferrocenylmethylnitroanilines as Potential Anticancer Drugs

2016 ◽  
Vol 2 ◽  
pp. 5-12 ◽  
Author(s):  
Touhami Lanez ◽  
Elhafnaoui Lanez
Keyword(s):  
Escherichia Coli ◽  
Molecular Docking ◽  
Protein Structure ◽  
Dna Gyrase ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Molegro Virtual Docker ◽  
Gyrase A

In the present study, the interaction of the protein structure of Escherichia coli DNA Gyrase-A (EcGyr-A) extracted from protein data bank (PDB Code: 1AB4) with ligands N-ferrocenylmethyl-2-nitroaniline (2FMNA), N-ferrocenylmethyl-3-nitroaniline (3FMNA) and N-ferrocenylmethyl-4-nitroaniline (4FMNA) were investigated by performing docking studies using the Molegro Virtual Docker (MVD) software. The results obtained showed that the best poses which is derived from MolDock score for Escherichia coli DNA Gyrase-A were respectively equal to-92.0111, -96.0866 and-95.6808 with reranking score equal to-40.9575, -73.4476 and-73.6423. Calculations revealed that 3FMNA react strongly with EcGyr-A followed by 4-FMNA and 2-FMNA.

scholarly journals MOLECULAR DOCKING STUDY ON 1H-(3,4d) PYRAZOLO-PYRIMIDINES AS CYCLIN DEPENDANT KINASE (CDK2) INHIBITORS

2016 ◽  
Vol 9 (1) ◽  
pp. 94
Author(s):  
Manisha S. Phoujdar ◽  
Gourishankar R. Aland
Keyword(s):  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Van Der Waals Interactions ◽  
Binding Modes ◽  
Molecular Docking Study ◽  
Discovery Studio ◽  
Receptor Assays

Objective: CDK2 inhibitors are implicated in several carcinomas viz. Carcinoma of lung, bladder, sarcomas and retinoblastoma. Pyrazolopyrimidines, being purine bioisosters inhibit more than one type of kinase. In this study, we are studying some novel derivatives of 1H-pyrazolo [3,4d] pyrimidines not reported earlier. The objective of the present study is an attempt towards design and development of 1H-[3,4-] pyrazolo-pyrimidines as CDK2 inhibitors through rational drug design.Methods: The present study has been done on CDK2 structure, PDB ID, 3WBL, co-crystallized with ligand PDY from RCSB protein data bank. A series of seventeen 1H-Pyrazolo [3,4-d] pyrimidines feasible for synthesis was docked on the said CDK2 receptor using Auto Dock 4 version, 1.5.6. Outputs were exported to discovery studio 3.5 client for visual inspection of the binding modes and interactions of the compounds with amino acid residues in the active sites.Results: The results of docking studies revealed that the present series of 1H-Pyrazolo[3,4-d] pyrimidines is showing significant binding through hydrogen bonding, hydrophobic, pi and Van der waals interactions, similar to the ligand PDY. Some conserved H-bond interactions comparable to bioisosters and compounds presently under human trials were noted. Ki values predicted in silico also suggest that the series will show promising CDK2 inhibitory activity.Conclusion: The series designed and docked can be further developed by synthesis and in vitro and in vivo activity. The receptor inhibitory activity can also be checked by specific receptor assays.

Potential Bioactive glycosylated flavonoids as SARS-CoV-2 Main protease Inhibitors: A molecular Docking Study

2020 ◽  
Author(s):  
sabri ahmed cherrak ◽  
merzouk hafida ◽  
mokhtari soulimane nassima
Keyword(s):  
Molecular Docking ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
In Vivo Experiments ◽  
Main Protease

A novel (COVID-19) responsible of acute respiratory infection closely related to SARS-CoV has recently emerged. So far there is no consensus for drug treatment to stop the spread of the virus. Discovery of a drug that would limit the virus expansion is one of the biggest challenges faced by the humanity in the last decades. In this perspective, testing existing drugs as inhibitors of the main COVID-19 protease is a good approach.Among natural phenolic compounds found in plants, fruit, and vegetables; flavonoids are the most abundant. Flavonoids, especially in their glycosylated forms, display a number of physiological activities, which makes them interesting to investigate as antiviral molecules.The flavonoids chemical structures were downloaded from PubChem and protease structure 6lu7 was from the Protein Data Bank site. Molecular docking study was performed using AutoDock Vina. Among the tested molecules Quercetin-3-O-rhamnoside showed the highest binding affinity (-9,7 kcal/mol). Docking studies showed that glycosylated flavonoids are good inhibitors for the covid-19 protease and could be further investigated by in vitro and in vivo experiments for further validation.

scholarly journals Molecular Docking Analysis of Ginger Active Compound on Transient Receptor Potential Cation Channel Subfamily V Member 1 (TRPV1)

2018 ◽  
Vol 18 (1) ◽  
pp. 179 ◽  
Author(s):  
Fifteen Aprila Fajrin ◽  
Agung Endro Nugroho ◽  
Rina Susilowati ◽  
Arief Nurrochmad
Keyword(s):  
Binding Energy ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Data Bank ◽  
Docking Study ◽  
Cation Channel ◽  
Active Compounds ◽  
Docking Analysis ◽  
Transient Receptor ◽  
Native Ligand

Ginger had been reported to ameliorate painful diabetic neuropathy (PDN) in an animal model. Gingerol and shogaol were active compounds of ginger that potentially act on transient receptor potential cation channel subfamily V member 1 (TRPV1), a key receptor in PDN. This study aims to predict the binding of gingerol and shogaol to TRPV1 using an in silico model. The ligands of the docking study were 3 chemical compounds of each gingerol and shogaol, i.e. 6-shogaol, 8-shogaol, 10-shogaol, 6-gingerol, 8 gingerol and 10-gingerol. Capsaicin, a TRPV1 agonist, was used as a native ligand. The TRPV1 structure was taken from Protein Data Bank (ID 3J9J). The docking analysis was performed using Autodock Vina. The result showed that among the ginger active compounds, 6-shogaol had the strongest binding energy (-7.10 kcal/mol) to TRPV1. The 6-shogaol lacked the potential hydrogen bond to Ile265 of TRPV1 protein, which capsacin had. However, it's binding energy towards TRPV1 was not significantly different compared to capsaicin. Therefore, 6-shogaol had potential to be developed as a treatment for PDN.

scholarly journals Repurposing Hydroxychloroquine as a Model Drug for the Prediction of Potential SARS-CoV-2 Inhibitor

2020 ◽  
Vol 5 (9) ◽  
pp. 1031-1036
Author(s):  
K. K. Igwe ◽  
O. V. Ikpeazu ◽  
F. J. Amaku ◽  
I. E. Otuokere
Keyword(s):  
Clinical Trials ◽  
Molecular Docking ◽  
Binding Energy ◽  
Virtual Screening ◽  
Docking Studies ◽  
Drug Candidate ◽  
Lead Compound ◽  
Toxicity Prediction ◽  
Zinc Database ◽  
Model Drug

The use of hydroxychloroquine as SARS-CoV-2 inhibitor is currently being reviewed in various clinical trials.  To exhaustively assess the benefit of hydroxychloroquine in the search for SARS-CoV-2 cure, this paper repositioned hydroxychloroquine as a model for virtual screening on the ZINC database.  Molecular docking studies of 5r7y with the retrieved molecules were performed.  The S-score of the predicted compounds were compared with the reference inhibitor (hydroxychloroquine).  After evaluating their binding energy, five compounds (ZINC52939663, ZINC21291670, ZINC12714071, ZINC40089978 and ZINC15963294) were noticed have to highest binding energy with SARS-CoV-2.  The binding scores of the top five ligands were higher than that of the reference molecule.  The pharmacokinetics, toxicity prediction, drug-likeness and global reactivity assessment of ZINC52939663, present the lead compound as a drug candidate with the probable capacity to inhibit SARS-CoV-2.

scholarly journals Synthesis, molecular docking studies, and antimicrobial evaluation of pyrano[2, 3-c]pyrazole derivatives

2021 ◽  
pp. 309-328 ◽  
Author(s):  
Samy A. El-Assaly ◽  
Abd El-Hamid A. Ismail ◽  
Hamed Abdel Bary ◽  
Mohamed G. Abouelenein
Keyword(s):  
Molecular Docking ◽  
Binding Protein ◽  
Diethyl Malonate ◽  
Docking Study ◽  
Docking Studies ◽  
Penicillin Binding Protein ◽  
Molecular Docking Study ◽  
One Pot ◽  
Bacterial Action ◽  
Potential Mode

A sequence of pyrano[2, 3-c]pyrazoles was constructed through promoting an eco-friendly, green, and efficient approach. M1-M25 derivatives were developed by a base-catalyzed one-pot reaction involving application of hydrazine hydrate 96%, β-keto ester as ethyl acetoacetate or diethyl malonate, aryl/heteroaryl aldehyde or isatin, and enolizable active methylene compounds with isolation of unexpected compound M2. Further on, intramolecular cyclization of compounds M10, M13 with formic acid, acetic anhydride, and formamide leads to the corresponding pyrimidine derivatives M26-M31. Afterwards, the antimicrobial activity of the compounds was evaluated and fortunately, the vast majority of the compounds showed outstanding anti-bacterial results. Besides, the potential mode of action of the synthesized compounds was determined by employing a molecular-docking study against penicillin-binding protein implicated in anti-bacterial action. Compound M21 was one of the most promising anti-bacterial agents with potential binding affinity against the penicillin-binding protein. This study shed light on novel compounds for further antimicrobial drug development.

scholarly journals Molecular Docking Study of Astaxanthin Derived from Radio-Resistant Bacterium Deinococcus sp. Strain WMA-LM9 to Matrix Metalloproteinase-1, 3 (MMP-1, MMP-3)

2021 ◽  
Vol 2 (1) ◽  
pp. 6
Author(s):  
Wasim Sajjad ◽  
Sumra Wajid Abbasi ◽  
Liaqat Ali
Keyword(s):  
Matrix Metalloproteinases ◽  
Hydrophobic Interactions ◽  
Data Bank ◽  
Docking Study ◽  
Zinc Ion ◽  
Skin Aging ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Matrix Metalloproteinase 1 ◽  
National University

Objective: To assess role of astaxanthin in downregulation of matrix metalloproteinases (MMP-1 and MMP-3) as potential mitigator for skin aging and antioxidant for different pathological diseasesStudy Design: Cross sectional.Place and Duration of Study: The study was carried out at Department of Biological Sciences of National University of Medical Sciences, Rawalpindi, Pakistan from June 2019 to March 2020.Materials and Methods: The docking studies of two different matrix metalloproteinases (MMP-1, MMP-3) with astaxanthin were carried out using Autodock/vina. The structural details were obtained from protein data bank and subjected to energy minimization using the UCSF Chimera 1.12.|Results: Out of the two selected targets, we found the highest binding energy (-11.9 kacl/mol) was for stromelysin-1 and astaxanthin docked complex. Astaxanthin was found to bind within the reported, predominantly hydrophobic S1, active site of protein mostly by hydrophobic interactions. The catalytic zinc ion has also shown to establish an electrostatic interaction with histidine residues of the MMPs.Conclusion: The current results suggest that astaxanthin has potential inhibitory activity on MMP-1 and MMP-3 and can be used as treatment to sunburns and skin aging.

scholarly journals A Molecular Docking Study against COVID-19 Protease with a Pomegranate Phyto-Constituents 'Urolithin' and Other Repurposing Drugs: From a Supplement to Ailment

2020 ◽  
pp. 51-62
Author(s):  
Varish Ahmad
Keyword(s):  
Binding Energy ◽  
Antimicrobial Agents ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Discovery Studio ◽  
Urolithin A ◽  
In Silico Study ◽  
Drug Compounds ◽  
Urolithin B

Aim: We conducted an in silico study on Urolithin and different antimicrobial agents targeting virus protease and peptidase. Methodology: The docking study was completed by using docking tools. Drug compounds and COVID-19 receptor molecules were prepared, docking was performed and interaction was visualized through Discovery Studio visualizer. Results: Urolithin A has interacted against peptidase (PDB ID:2GTB) with binding energy -6.93 kcal/mol and against protease (PDB ID:6LU7) with  the binding energy -5.46 kcal/mol, while Urolithin B has interacted to peptidase (PDB ID:2GTB)  with binding energy -6.74 kcal/mol  and with protease it interacted with a binding energy -4.67 kcal/mol. The antimicrobial agent Ofloxacin was found to interact against protease (PDB ID:6LU7) with a binding energy -6.84 kcal/mol and  against protease (PDB:6LU7)  with a binding energy -8.00 kcal/mol. Conclusion: The most common interacting amino acids of target enzymes of the virus with studied drugs were His41, His164, Met165, Glu166, Gln189. From the docking studies, it is observed that Ofloxacin and Urolithin have the potential to inhibit the virus protease as well as peptidase significantly and these could prevent the entry of the virus to the inside of the host cell. Thus, further antiviral research on these antimicrobial agents and Urolithin could be helpful to control the COVID-19 disease.

Sign in / Sign up

Export Citation Format

Share Document