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.

scholarly journals MOLECULAR DOCKING STUDY OF NATURALLY OCCURRING COMPOUNDS AS INHIBITORS OF COVID -19

2021 ◽  
pp. 69-71
Author(s):  
SREEDEVI A ◽  
MALAR RETNA A ◽  
ROBIN KUMAR SAMUEL
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Discovery Studio ◽  
Naturally Occurring ◽  
Short Period ◽  
The Right ◽  
Native Ligand ◽  
Made In

Objectives: The worldwide spread of COVID-19 is an emergent issue to be tackled. Currently, several works in various field have been made in rather short period. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 Mpro inhibitors using molecular docking study. Methods: The docking analyses were performed by using Autodock, Discovery Studio Visualiser and Igemdock. Results: The binding energy obtained from the docking of 6LU7 with native ligand cupressuflavone is -8.9 kcal/mol. Conclusion: These findings will provide the opportunities to identify the right drug to combat COVID-19.

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.

Pyridine and Benzoisothiazole Decorated Vanillin Chalcones: Synthesis, Antimicrobial, Antioxidant, Molecular Docking Study and ADMET Properties

2020 ◽  
Vol 17 (5) ◽  
pp. 367-381
Author(s):  
Pintu Pathare ◽  
Sunil Tekale ◽  
Rafique Shaikh ◽  
Manoj Damale ◽  
Jaiprakash Sangshetti ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Docking Study ◽  
Docking Studies ◽  
Pharmacokinetic Parameters ◽  
Molecular Docking Study ◽  
Antimicrobial Drugs ◽  
Discovery Studio ◽  
Pharmacokinetic Properties

Background: The search for new antimicrobial drugs is a never ending task due to microbial resistance to the existing drugs. Antioxidants are essential to prevent free radical reactions which lead to chronic diseases to human kind. Objective: The present studies were aimed to synthesis, characterization, antimicrobial and antioxidant activities of pyridine and benzoisothiazole decorated chalcones. Materials and Methods: FTIR spectra were recorded using KBr pellets on Shimadzu FT-IR spectrophotometer. 1H and 13C NMR spectra were recorded on Bruker 400 MHz spectrometer. Antimicrobial activity of the synthesized chalcones was found to be good against diffenet bacterial and fungal strains. Antioxidant activity was studied in terms of 2,2-diphenyl-1-picrylhydrazyl, hydroxyI and superoxide radical scavenging activities. Molecular docking was studied using Discovery Studio Visualizer Software, version 16 whereas Autodock Vina program was used to predict toxicity profile of the compounds using FAFDrugs2 predictor. Results: The compounds 5c, 5d & 6c showed good antioxidant activities. The insilico molecular docking study supports the experimental results and demonstrated that the chalcones 5d, 6a and 7a are the most active among the synthesized derivatives. Conclusion: Prediction of pharmacokinetic parameters and molecular docking studies suggest that the synthesized chalcones have good pharmacokinetic properties to act as lead molecules in the drug discovery process.

scholarly journals A Comparative Study of Approved Drugs for SARS-CoV-2 by Molecular Docking

2021 ◽  
Vol 1 (1) ◽  
pp. 25-31
Author(s):  
Achal Mishra ◽  
Radhika Waghela
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Docking Studies ◽  
Target Protein ◽  
Molecular Docking Study ◽  
Discovery Studio ◽  
Drug Molecules ◽  
Main Protease ◽  
New Type ◽  
Approved Drugs

SARS-CoV-2, a new type of Coronavirus, has affected more millions of people worldwide. From the spread of this infection, many studies related to this virus and drug designing for the treatment have been started. Most of the studies target the SARS-CoV-2 main protease, spike protein of SASR-CoV-2, and some are targeting the human furin protease. In the current work, we chose the clinically used drug molecules remdesivir, favipiravir, lopinavir, hydroxychloroquine, and chloroquine onto the target protein SARS-CoV-2 main protease. Docking studies were performed using Arguslab, while Discovery Studio collected 2D and 3D pose views with the crystal structure of COVID-19 main protease in complex with an inhibitor N3 with PDB ID 6LU7. Computational studies reveal that all ligands provided good binding affinities towards the target protein. Among all the chosen drugs, lopinavir showed the highest docking score of -11.75 kcal/mol. The results from this molecular docking study encourage the use of lopinavir as the first-line treatment drug due to its highest binding affinity.

Molecular modeling of substances isolated from the essential oil of the species Drimys angustifolia and Drimys brasiliensis

2020 ◽  
Vol 10 ◽  
Author(s):  
Neuziane Dias Conceição ◽  
Lucilene Rocha de Souza ◽  
Jaderson Vieira Ferreira ◽  
Maiara de Fátima Brito Brito ◽  
Abraão Alves Pinheiro ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Chemical Reactivity ◽  
Skin Permeation ◽  
Docking Study ◽  
Docking Studies ◽  
Skin Permeability ◽  
Molecular Docking Study ◽  
Molecular Stability ◽  
In Silico Study ◽  
Drimys Brasiliensis

Objectives: Carry out an in silico study of chemical substances isolated from the species Drimys angustifolia and Drimys brasiliensis. Methods: A theoretical study of global reactivity and QSAR descriptors, MEP construction, molecular docking study was performed to analyze the interaction of substances with acetylcholinesterase of Drosophila melanogaster and prediction of skin permeation and toxicological properties of the substances. Results: The chemical reactivity and molecular stability investigation proposed that the substance which presented stability values similar to the standard substance D-limonene was the substance Terpinen-4-ol. The MEPs of the investigated substances were evenly distributed along the hydrogens and oxygens. In molecular docking studies here performed, the substance Myristicin showed interesting and promising results. Regarding to skin permeability, all substances showed low absorbed by the skin, in potential. For toxicological properties, the substance Bicyclogermacrene showed non-carcinogenicity and mutagenicity activity. Conclusion: Thus, it was possible to determine that the substance Bicyclogermacrene presented suitable results for future use as a repellent candidate..

scholarly journals In-silico molecular docking study of some n-substituted thiazoles derivatives as FabH inhibitors

2020 ◽  
Vol 8 (2) ◽  
pp. 043-055
Author(s):  
Shivkant Sharma ◽  
Manish Devgun ◽  
Karan Wadhwa ◽  
Sahil Banwala
Keyword(s):  
Hydrogen Bonding ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Docking Study ◽  
Thiazole Derivatives ◽  
Molecular Docking Study ◽  
Molegro Virtual Docker ◽  
In Silico Study ◽  
In Silico Molecular Docking ◽  
Therapeutic Activities

Heterocyclic compounds with thiazole moiety are one of the most promising compounds in the medicinal chemistry possessing numerous therapeutic activities. The present was designed to study the high throughput in silico screening of 10 designed 2-phenyl-amino thiazole derivatives as a potent FABH inhibitor in Molegro virtual docker software (Version 6.0) using 3iL9 as PDB. The docking results showed mol dock score of -90.94 with four hydrogen bonding for the standard drugs griseofulvin, while on the other hand, N-substituted thiazole derivatives S2, S5, S6, S7, S8, and S9 exhibited excellent mol dock score, ranged from -102.612 to -144.236, hydrogen bonding (4-10), and docking score ranged from -104.873 to -143.593. Similarly, another in silico study was done using online PASS software and the compounds S1, S2, S5, S6, S7, S8, and S9 have Pa ranged between 0.310 to 0.411 and showed good antibacterial activity whereas, compounds having Pa ranged between 0.216 to 0.334 demonstrated potent antifungal activity when compared to standard drugs. Thus, the present study affirmed the significant antimicrobial potential of some designed N-substituted thiazole derivatives based on their mol dock values and other parameters when studies in silico and the obtained results will provide data support and offer perspectives in future researches to develop potent antimicrobial agents from these N-substituted thiazole derivatives.

Synthesis, docking and antimicrobials evaluation of novel pyrazolotriazines as RNA polymerase inhibitors

2021 ◽  
Vol 25 ◽  
Author(s):  
Amira Abdallah ◽  
Galal Elgemeie ◽  
Ebtsa Ahmed
Keyword(s):  
Rna Polymerase ◽  
Antimicrobial Agents ◽  
Inhibitory Concentration ◽  
Acid Synthesis ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Synthetic Compound ◽  
Polymerase Beta ◽  
Cell Wall Inhibition

: A series of novel pyrazolo[1,5-a][1,3,5]triazine and pyrazolo[5,1-c][1,2,4]triazine, were synthesized from the 5-aminopyrazoles 3, which was previously prepared and considered a starting precursor for synthesizing many promising bioactive compounds. Thus, all the prepared compounds were evaluated as antimicrobial agents. Also, the minimum inhibitory concentration (MIC) for the most potent compounds was measured. Moreover, docking studies were performed using the newly prepared compounds to evaluate their affinity to different bacterial target proteins with varying modes of action involving cell wall inhibition, protein and nucleic acid synthesis, and antimetabolites. Some of the prepared compounds revealed potent activity towards some of the bacterial and fungal strains used. After molecular docking study validation, it seemed that the synthetic compound mode of action was through RNA synthesis inhibition, while the DNA-dependant RNA polymerase beta subunit repC (PDB: 2AUK) was the probable protein target. The RNA polymerase inhibitory activity was measured for the most potent antimicrobial compounds with high docking scores for more evidence.

Design, Synthesis, Antimicrobial and Anti-biofilm Evaluation, and Molecular Docking of Newly Substituted Fluoroquinazolinones

2019 ◽  
Vol 15 (6) ◽  
pp. 659-675
Author(s):  
Mohamed F. Zayed ◽  
Sabrin R.M. Ibrahim ◽  
EL-Sayed E. Habib ◽  
Memy H. Hassan ◽  
Sahar Ahmed ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Receptor Site ◽  
Docking Study ◽  
Diffusion Method ◽  
Molecular Docking Study ◽  
Active Compounds ◽  
Highly Active ◽  
Strong Binding ◽  
Agar Disc

Background: Quinazolines and quinazolinones derivatives are well known for their important range of therapeutic activities. Objective: The study aims to carry out the synthesis of some derivatives of substituted fluoroquinazolinones based on structure-based design and evaluation of their antibacterial, antifungal, and anti-biofilm activities. Methods: Compounds were chemically synthesized by conventional methods. Structures were established on the basis of spectral and elemental analyses. The antimicrobial potential was tested against various microorganisms using the agar disc-diffusion method. MIC and MBC as well as anti-biofilm activity for the highly active compounds were assessed. Moreover, the computational studies were performed using Auto dock free software package (version 4.0) to explain the predicted mode of binding. Results: All derivatives (5-8), (10a-g), and (A-H) were biologically tested and showed significant antimicrobial activity comparable to the reference compounds. Compounds 10b, 10c, and 10d had a good MIC and MBC against Gram-positive bacteria, whereas 10b and 10d showed significant MIC and MBC against Gram-negative bacteria. However, compounds E and F exhibited good MIC and MBC against fungi. Compound 10c and 8 exhibited significant anti-biofilm activity towards S. aureus and M. luteus. Molecular docking study revealed a strong binding of these derivatives with their receptor-site and detected their predicted mode of binding. Conclusion: The synthesized derivatives showed promising antibacterial, antifungal, and antibiofilm activities. Modeling study explained their binding mode and showed strong binding affinity with their receptor-site. The highly active compounds 5 and 10c could be subjected to future optimization and investigation to be effective antimicrobial agents.

scholarly journals Interaction between DNA, Albumin and Apo-Transferrin and Iridium(III) Complexes with Phosphines Derived from Fluoroquinolones as a Potent Anticancer Drug

2021 ◽  
Vol 14 (7) ◽  
pp. 685
Author(s):  
Sandra Amanda Kozieł ◽  
Monika Katarzyna Lesiów ◽  
Daria Wojtala ◽  
Edyta Dyguda-Kazimierowicz ◽  
Dariusz Bieńko ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Serum Proteins ◽  
Docking Study ◽  
Minor Groove ◽  
Docking Studies ◽  
Minor Groove Binding ◽  
Binding Modes ◽  
Groove Binding ◽  
Molecular Docking Study ◽  
Threading Intercalation

A group of cytotoxic half-sandwich iridium(III) complexes with aminomethyl(diphenyl)phosphine derived from fluoroquinolone antibiotics exhibit the ability to (i) accumulate in the nucleus, (ii) induce apoptosis, (iii) activate caspase-3/7 activity, (iv) induce the changes in cell cycle leading to G2/M phase arrest, and (v) radicals generation. Herein, to elucidate the cytotoxic effects, we investigated the interaction of these complexes with DNA and serum proteins by gel electrophoresis, fluorescence spectroscopy, circular dichroism, and molecular docking studies. DNA binding experiments established that the complexes interact with DNA by moderate intercalation and predominance of minor groove binding without the capability to cause a double-strand cleavage. The molecular docking study confirmed two binding modes: minor groove binding and threading intercalation with the fluoroquinolone part of the molecule involved in pi stacking interactions and the Ir(III)-containing region positioned within the major or minor groove. Fluorescence spectroscopic data (HSA and apo-Tf titration), together with molecular docking, provided evidence that Ir(III) complexes can bind to the proteins in order to be transferred. All the compounds considered herein were found to bind to the tryptophan residues of HSA within site I (subdomain II A). Furthermore, Ir(III) complexes were found to dock within the apo-Tf binding site, including nearby tyrosine residues.

Selection of oxypeucedanin as a potential antagonist from molecular docking analysis of HSP90

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Joshua Oluwasegun Bamidele ◽  
George Oche Ambrose ◽  
Oluwaseun Suleiman Alakanse
Keyword(s):  
Molecular Docking ◽  
Liver Toxicity ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Computational Docking ◽  
Drug Candidates ◽  
Expression Rate ◽  
Client Proteins

AbstractHSP90 is observed as one of the copious molecular chaperones that play a key role in mediating appropriate folding, maturation, and firmness of many client proteins in cells. The expression rate of HSP90 in cancer cells is at a level of 2- to 10-fold higher than the 1- to 2-fold of its unstressed and healthy ones. To combat this, several inhibitors to HSP90 protein have been studied (such as geldanamycin and its derivative 17-AAG and 17-DMAG) and have shown some primary side effects including plague, nausea, vomiting, and liver toxicity, hence the search for the best-in-class inhibitor for this protein through in silico. This study is aimed at analyzing the inhibitory potency of oxypeucedanin-a furocoumarin derivations, which have been reported to have antipoliferative activity in human prostrate carcinoma DN145 cells, and three other drug candidates retrieved from the literature via computational docking studies. The results showed oxypeucedanin as the compound with the highest binding energy of −9.2 kcal/mol. The molecular docking study was carried out using PyRx, Auto Dock Vina option, and the target was validated to confirm the proper target and the docking procedure employed for this study.

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