scholarly journals Biological activity, molecular docking, and ADME predictions of amphibine analogues of Ziziphus spina-christi towards SARS-CoV-2 Mpro

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Taufik Muhammad Fakih ◽  
Dwi Syah Fitra Ramadhan ◽  
Fitrianti Darusman
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Binding Energy ◽  
Docking Simulation ◽  
Oral Drug ◽  
Molecular Docking Simulation ◽  
Main Protease ◽  
Promising Target ◽  
Quantum Espresso ◽  
Native Ligand

The main protease of the SARS-CoV-2 virus, SARS-CoV-2 Mpro, can be discovered as a promising target to treat the COVID-19 pandemic. The peptide-based inhibitors may present better options than small molecules for inhibits SARS-CoV-2 Mpro. Ziziphus spina-christi species reported have a peptide-based of alkaloids group, i.e. Amphibine that the analogues can be identified the potential as an inhibitor of SARS-CoV-2 Mpro. The compound structure was drawn and optimized using semi-empirical AM-1 method using Quantum ESPRESSO v.6.6, then the biological activity using PASS Prediction server and molecular docking simulation using MGLTools 1.5.6 with AutoDock 4.2 were performed. Afterward, the ADME profiles were predicted using the SWISS-ADME server. PASS server was predicting Amphibine B-F and H showed potency both as antiviral and as a protease inhibitor. The molecular docking simulation of Amphibine analogues showed lower binding energy than the native ligand. The binding energy of the native ligand was −7.69 Kcal/mol compared to the lowest binding energy of Amphibine analogues was −10.10 Kcal/mol (Amphibine-F). The ADME prediction showed, as an oral drug Amphibine-F has the best bioavailability, Amphibine-B, C, and D have good bioavailability, and Amphibine-E and H have poor bioavailability. Concluded, Amphibine B-F and H of Amphibine analogues showed potency as COVID-19 treatment targeting SARS-CoV-2 Mpro.

Quantitative structure-activity relationship model, molecular docking simulation and computational design of some novel compounds against DNA gyrase receptor.

2020 ◽  
Vol 16 ◽  
Author(s):  
Shola Elijah Adeniji
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Binding Energy ◽  
Biological Activities ◽  
Docking Simulation ◽  
Dna Gyrase ◽  
Computational Design ◽  
Multi Drug Resistance ◽  
Drug Candidate ◽  
Standard Drug

Introduction: Mycobacterium tuberculosis has instigated a serious challenge toward the effective treatment of tuberculosis. The reoccurrence of the resistant strains of the disease to accessible drugs/medications has mandate for the development of more effective anti-tubercular agents with efficient activities. Time expended and costs in discovering and synthesizing new hypothetical drugs with improved biological activity have been a major challenge toward the treatment of multi-drug resistance strain M. tuberculosis (TB). Meanwhile, to solve the problem stated, a new approach i.e. QSAR which establish connection between novel drugs with a better biological against M. tuberculosis is adopted. Methods: The anti-tubercular model established in this study to forecast the biological activities of some anti-tubercular compounds selected and to design new hypothetical drugs is subjective to the molecular descriptors; MATS7s, SM1_DzZ, SpMin4_Bhv, TDB3v and RDF70v. Ligand-receptor interactions between quinoline derivatives and the receptor (DNA gyrase) was carried out using molecular docking technique by employing the PyRx virtual screening software and discovery studio visualizer software. Furthermore, docking study indicates that compounds 20 of the derivatives with promising biological activity have the utmost binding energy of -17.79 kcal/mol. Results: Meanwhile, the interaction of the standard drug; isoniazid with the target enzyme was observed with the binding energy -14.6 kcal/mol which was significantly lesser than the binding energy of the ligand (compound 20).Therefore, compound 20 served as a template structure to designed compounds with more efficient activities. Among the compounds designed; compounds 20p was observed with better anti-tubercular activities with more prominent binding affinities of -24.3kcal/mol. Conclusion: The presumption of this research aid the medicinal chemists and pharmacist to design and synthesis a novel drug candidate against the tuberculosis. Moreover, in-vitro and in-vivo test could be carried out to validate the computational results.

Potential Leads from Liquorice against SARS-CoV-2 Main Protease using Molecular Docking Simulation Studies

2020 ◽  
Vol 23 ◽  
Author(s):  
Saurabh K. Sinha ◽  
Satyendra K. Prasad ◽  
Md Ataul Islam ◽  
Sushil K. Chaudhary ◽  
Shashikant Singh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Glycyrrhizic Acid ◽  
Docking Simulation ◽  
Simulation Studies ◽  
Autodock Vina ◽  
Molecular Docking Simulation ◽  
Global Pandemic ◽  
Main Protease ◽  
Pandemic Threat ◽  
Inhibitory Potential

Aim and Objective: At present, the world is facing a global pandemic threat of SARS-CoV-2 or COVID-19 and till date, there are no clinically approved vaccines or antiviral drugs available for the treatment of coronavirus infections. Studies conducted in China recommended the use of liquorice (Glycyrrhiza species), an integral medicinal herb of traditional Chinese medicine in the deactivation of COVID-19. Therefore, the present investigation was undertaken to identify the leads from the liquorice plant against COVID-19 using molecular docking simulation studies. Materials and Methods: A set of reported bioactive compounds of liquorice were investigated for COVID-19 main protease (Mpro) inhibitory potential. The study was conducted on Autodock vina software using COVID-19 Mpro as a target protein having PDB ID: 6LU7. Results: Out of the total 20 docked compounds, only six compounds showed the best affinity towards the protein target, which included glycyrrhizic acid, isoliquiritin apioside, glyasperin A, liquiritin, 1-methoxyphaseollidin and hedysarimcoumestan B. From the overall observation, glycyrrhizic acid followed by isoliquiritin apioside demonstrated the best affinity towards Mpro representing the binding energy of -8.6 and -7.9 Kcal/mol respectively. Nevertheless, the other four compounds were also quite comparable with the later one. Conclusion: From the present investigation, we conclude that the compounds having oxane ring and chromenone ring substituted with hydroxyl 3-methylbut-2-enyl group could be the best alternative for the development of new leads from liquorice plant against COVID-19.

scholarly journals In Silico Activity Identification of Cyclo Peptide Alkaloids from Zizyphus Spina-Christi Species Against Sars-Cov-2 Main Protease

2021 ◽  
Vol 6 (1) ◽  
pp. 71-81
Author(s):  
Taufik Muhammad Fakih ◽  
Dwi Syah Fitra Ramadhan ◽  
Fitrianti Darusman
Keyword(s):  
In Silico ◽  
Density Functional ◽  
Docking Simulation ◽  
Functional Theory ◽  
Main Protease ◽  
Docking Method ◽  
Promising Target ◽  
Cyclopeptide Alkaloids ◽  
Prediction Server ◽  
Native Ligand

The COVID-19 has spread worldwide and become an international pandemic. The promising target for drug discovery of COVID-19 was SARS-CoV-2 Main Protease (Mpro), that has been successfully crystallized along with its inhibitor. The discovery of peptide-based inhibitors may present better options than small molecules for inhibitor SARS-CoV-2 Mpro. Natural compounds have such a wide potential and still few explored, Zizyphus spina-christi is one of the medicinal plants that have many pharmacological activities and contains a peptide compound from alkaloids class, i.e. cyclopeptide alkaloids, that is interesting to explore as SARS-CoV-2 Mpro inhibitor. The compound structure was drawn and optimized using density functional theory 3-21G method. The protein chosen was the high resolution of SARS-CoV-2 MPro receptor (1.45 Å) with PDB ID: 6WNP, in complex with boceprevir. Molecular docking simulation was performed using Autodock4 with 100 numbers of GA run, the validation methods assessed by RMSD calculation. Furthermore, the prediction of pharmacological activity spectra was carried out using the PASS Prediction server. The results showed RMSD value was 1.98 Å, this docking method was valid. The binding energy of all compounds showed better results than the native ligand (Boceprevir). The in silico PASS prediction results indicated that all compounds showed antiviral activity. Some compounds showed protease inhibitory activity, i.e Ambiphibine-H, Franganine, and Mauritine-A, and the highest Pa (Predicted activity) value showed by Mauritine-A compounds. It can be concluded that the cyclopeptide compounds of Zizyphus spina-christi were indicated to have a potential as COVID-19 therapy targeting SARS-CoV-2 Mpro.

Design, Molecular docking, Synthesis and Biological evaluation of 5, 7 dimethyl pyrido(2, 3-d)pyrimidin-4-one and 4,5 dihydro pyrazolo (3, 4-d) pyrimidines for cytotoxic activity

2021 ◽  
pp. 3029-3038
Author(s):  
M. Sathish Kumar ◽  
M. Vijey Aanandhi
Keyword(s):  
Molecular Docking ◽  
Docking Simulation ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Hep G2 ◽  
Molecular Docking Simulation ◽  
Hela Cell Lines ◽  
Benzene Diazonium ◽  
Synthesis And Biological Evaluation ◽  
Mcf 7

The fused pyrimidine derivatives are potent tyrosine kinase and thymidylate synthase inhibitors. The compound 3-(4-sulphonyl amino)-2-methyl thio-6-phenyl azo-5, 7-dimethyl pyrido(2,3-d)pyrimidin-4-one was synthesized from Ethyl 2-amino-4,6-dimethylpyridine-3-carboxylate, benzene diazonium chloride, benzene sulphonyl amino isothiocyanate in subsequent reactions. 1-(1, 3-benzothiazol-2-yl)-3-methyl-4-phenyl-1H-pyrazolo[3,4-d]pyrimidines were synthesized from 1, 3-benzothiazole, 2-thiol, Hydrazine Hydrate, 2-hydrazinyl-1, 3-benzothiazole and aldehydes in subsequent reactions. Twenty-five derivatives pyrimidine scaffolds were designed and performed molecular docking studies for the ability to inhibit the target protein using molecular docking simulation, selective compounds were synthesized and characterized by spectral methods. All the synthesized compounds evaluated for their antioxidant activity and MTT assay exhibited compounds 13c, 13e and 14d can be potential anticancer candidates against MCF-7, Hep G2 and Hela cell lines respectively. Based on all the studies conclude that good agreement was observed between the top-ranked docking scores and top experimental inhibitors when compared with standards ascorbic acid and imatinib. Hence, the compounds could be considered as new anticancer hits for further lead optimization.

Binding Investigation of Integrin αvβ3 With Its Inhibitors by SPR Technology and Molecular Docking Simulation

2010 ◽  
Vol 15 (2) ◽  
pp. 131-137 ◽  
Author(s):  
Yaqin Liu ◽  
Yuanjiang Pan ◽  
Yuhong Xu
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Structural Model ◽  
Docking Simulation ◽  
Integrin Αvβ3 ◽  
Equilibrium Dissociation Constant ◽  
Molecular Docking Simulation ◽  
Spr Biosensor ◽  
Inhibitor Discovery ◽  
Equilibrium Dissociation

Integrins play critical roles in the process of angiogenesis and are attractive targets for anticancer therapies. It is desirable to develop new types of small-molecule inhibitors of integrin. Herein, the binding features of several inhibitors to integrin αvβ3 have been studied by surface plasmon resonance (SPR) biosensor technology and molecular docking analyses. The SPR results indicated that the equilibrium dissociation constant (KD) values are evaluated for the inhibitors and showed that the KD value of cyclopeptide c-Lys is much lower than the reference molecule. In addition, the 3D structural model of integrin αvβ3 was generated according to the crystal structure of the integrin αvβ3 complex, and the molecular docking simulation analyses revealed that the predicted binding sites for the most active cyclopeptide c-Lys were consistent with the reported structure. These results thus implied that cyclopeptide c-Lys could be developed as a novel inhibitor for integrin αvβ3. The current work has potential for application in structure-based integrin αvβ3 inhibitor discovery.

scholarly journals Discovery of GPX4 inhibitor by molecular docking simulation as a potential ferroptosis inducer

2020 ◽  
Vol 10 (1) ◽  
pp. 4929-4933
Keyword(s):  
Molecular Docking ◽  
Therapeutic Strategy ◽  
Docking Simulation ◽  
Drug Candidate ◽  
Synthetic Compounds ◽  
Molecular Docking Simulation ◽  
Docking Simulations ◽  
Lipinski’S Rule ◽  
Mercaptosuccinic Acid ◽  
Significant Public Health

As one of the most complex diseases in the world, cancer continues as one of the significant public health problems. It was recorded by 2014 that cancer caused 1,551,000 death in Indonesia. One type of programmed cell death (PCD) that played a role in cancer cell treatment is Ferroptosis. Ferroptosis is PCD on iron and characterized by the inactivation of glutathione-dependent peroxidase (GPx4). In this research, a new therapeutic strategy for cancer was developed through the computational approach on synthetic compounds to discover its potential as an inhibitor of GPx4. About 688 compounds derivative from mercaptosuccinic acid acquired from the Zinc15 database. These compounds screened through the Lipinski’s Rule of Three and pharmacological prediction to eliminate ligands with undesired molecular properties. After that, the ligands underwent both rigid and flexible molecular docking simulations to predict their inhibition activity toward GPx4. From molecular docking simulation, (2S)-2-[(Z)-3-phenylprop-2-enyl]sulfanylbutanedioic acid show favorable characteristics as a drug candidate.

PTP1B inhibitors from Selaginella tamariscina (Beauv.) Spring and their kinetic properties and molecular docking simulation

2017 ◽  
Vol 72 ◽  
pp. 273-281 ◽  
Author(s):  
Duc Dat Le ◽  
Duc Hung Nguyen ◽  
Bing Tian Zhao ◽  
Su Hui Seong ◽  
Jae Sue Choi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Simulation ◽  
Kinetic Properties ◽  
Molecular Docking Simulation ◽  
Selaginella Tamariscina ◽  
Ptp1b Inhibitors
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