scholarly journals An in-silico evaluation of different bioactive molecules of tea for their inhibition potency against non structural protein-15 of SARS-CoV-2

2021 ◽  
Vol 346 ◽  
pp. 128933
Author(s):  
Jatin Sharma ◽  
Vijay Kumar Bhardwaj ◽  
Rahul Singh ◽  
Vidya Rajendran ◽  
Rituraj Purohit ◽  
...  
Keyword(s):  
In Silico ◽  
Bioactive Molecules ◽  
Structural Protein ◽  
Inhibition Potency

Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies

2019 ◽  
Vol 15 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Paritosh Shukla ◽  
Ashok Sharma ◽  
Leena Fageria ◽  
Rajdeep Chowdhury
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bioactive Molecules ◽  
Microwave Assisted Synthesis ◽  
Binding Affinities ◽  
In Silico Docking

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

scholarly journals Comprehensive Virtual Screening of the Antiviral Potentialities of Marine Polycyclic Guanidine Alkaloids against SARS-CoV-2 (COVID-19)

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 460
Author(s):  
Amr El-Demerdash ◽  
Ahmed M. Metwaly ◽  
Afnan Hassan ◽  
Tarek Mohamed Abd El-Aziz ◽  
Eslam B. Elkaeed ◽  
...  
Keyword(s):  
In Silico ◽  
Active Sites ◽  
Specific Treatment ◽  
Aqueous Solubility ◽  
Maximum Tolerated Dose ◽  
Binding Energies ◽  
Log P ◽  
Binding Affinities ◽  
Structural Protein ◽  
Guanidine Alkaloids

The huge global expansion of the COVID-19 pandemic caused by the novel SARS-corona virus-2 is an extraordinary public health emergency. The unavailability of specific treatment against SARS-CoV-2 infection necessitates the focus of all scientists in this direction. The reported antiviral activities of guanidine alkaloids encouraged us to run a comprehensive in silico binding affinity of fifteen guanidine alkaloids against five different proteins of SARS-CoV-2, which we investigated. The investigated proteins are COVID-19 main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and a non-structural protein (nsp10) (PDB ID: 6W4H). The binding energies for all tested compounds indicated promising binding affinities. A noticeable superiority for the pentacyclic alkaloids particularly, crambescidin 786 (5) and crambescidin 826 (13) has been observed. Compound 5 exhibited very good binding affinities against Mpro (ΔG = −8.05 kcal/mol), nucleocapsid phosphoprotein (ΔG = −6.49 kcal/mol), and nsp10 (ΔG = −9.06 kcal/mol). Compound 13 showed promising binding affinities against Mpro (ΔG = −7.99 kcal/mol), spike glycoproteins (ΔG = −6.95 kcal/mol), and nucleocapsid phosphoprotein (ΔG = −8.01 kcal/mol). Such promising activities might be attributed to the long ω-fatty acid chain, which may play a vital role in binding within the active sites. The correlation of c Log P with free binding energies has been calculated. Furthermore, the SAR of the active compounds has been clarified. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) studies were carried out in silico for the 15 compounds; most examined compounds showed optimal to good range levels of ADMET aqueous solubility, intestinal absorption and being unable to pass blood brain barrier (BBB), non-inhibitors of CYP2D6, non-hepatotoxic, and bind plasma protein with a percentage less than 90%. The toxicity of the tested compounds was screened in silico against five models (FDA rodent carcinogenicity, carcinogenic potency TD50, rat maximum tolerated dose, rat oral LD50, and rat chronic lowest observed adverse effect level (LOAEL)). All compounds showed expected low toxicity against the tested models. Molecular dynamic (MD) simulations were also carried out to confirm the stable binding interactions of the most promising compounds, 5 and 13, with their targets. In conclusion, the examined 15 alkaloids specially 5 and 13 showed promising docking, ADMET, toxicity and MD results which open the door for further investigations for them against SARS-CoV-2.

scholarly journals In Silico Screening for Natural Ligands to Non-Structural Nsp7 Conformers of Coronaviruses

2020 ◽  
Author(s):  
Rafael Blasco ◽  
Julio Coll
Keyword(s):  
In Silico ◽  
Chemical Properties ◽  
Structural Similarity ◽  
Binding Pocket ◽  
Binding Affinities ◽  
Structural Protein ◽  
Autodock Vina ◽  
Natural Ligands ◽  
Final Optimization

<p>The non-structural protein 7 (nsp7) of Severe Acute Respiratory Syndrome (SARS) coronaviruses was selected as a new target to potentially interfere with viral replication. The nsp7s are one of the most conserved, unique and small coronavirus proteins having a critical, yet intriguing participation on the replication of the long viral RNA genome after complexing with nsp8 and nsp12. Despite the difficulties of having no previous binding pocket, two high-throughput virtual blind screening of 158240 natural compounds > 400 Da by AutoDock Vina against nsp7.1ysy identified 655 leads displaying predicted binding affinities between 10 to 1100 nM. The leads were then screened against 14 available conformations of nsp7 by both AutoDock Vina and seeSAR programs employing different binding score algorithms, to identify 20 consensus top-leads. Further <i>in silico</i> predictive analysis of physiological and toxicity ADMET criteria (chemical properties, adsorption, metabolism, toxicity) narrowed top-leads to a few drug-like ligands many of them showing steroid-like structures. A final optimization by search for structural similarity to the top drug-like ligand that were also commercially available, yielded a collection of predicted novel ligands with ~100-fold higher-affinity whose antiviral activity may be experimentally validated. Additionally, these novel nsp7-interacting ligands and/or their further optimized derivatives, may offer new tools to investigate the intriguing role of nsp7 on replication of coronaviruses.</p>

In silico drug design: development of new pyrimidine-based benzo-thiazole derivatives, selective for CDK2

2021 ◽  
Vol 18 ◽  
Author(s):  
Rania Kasmi ◽  
Larbi Elmchichi ◽  
Abdellah El Aissouq ◽  
Mohammed Bouachrine ◽  
Abdelkrim Ouammou
Keyword(s):  
Colon Cancer ◽  
Molecular Docking ◽  
In Silico ◽  
3D Qsar ◽  
Bioactive Molecules ◽  
Cancer Drugs ◽  
Qsar Studies ◽  
Benzothiazole Derivatives ◽  
Docking Approach ◽  
Potential Inhibitors

Backgroud: Kinases are proteins that control many biological functions. They are involved in cellular regulation, and many of them are deregulated in cancer proliferation. The evidence of this deregulation in many pathologies served as the origin of kinases as a therapeutic class and constitutes the motive that leads numerous teams to search for inhibitors of these targets. Objective: Based on 3D-QSAR studies and the molecular docking approach, we have developed new potential inhibitors that could be optimized and transformed into colon cancer drugs. Objective: Based on 3D-QSAR studies and the molecular docking approach, we have developed new potential inhibitors that could be optimized and transformed into colon cancer drugs. Method: To design new bioactive molecules and study their interactions with the cyclin-depend kinase type 2 (CDK2) enzyme, we used two virtual screening methods: 3D-QSAR modeling and molecular docking on a series of 28 pyrimidine-based benzothiazole derivatives. Results: To develop models (3D QSAR) we used CoMFA and CoMSIA techniques using SYBYL-X2.0 molecular modeling software. The statistical parameters reveal that the good CoMFA model displays (Q²= 0.587; R²= 0.895) and that of CoMSIA displays (Q²= 0.552; R²= 0.768) which are considered to be very good internal prediction values, while an external validation of a test series of 5 compounds not included in the model development series gives R²test values of 0.56 for CoMFA and R²test values of 0.51 for CoMSIA. The molecular docking approach with AutoDockTools-1.5.6 is introduced in this work to enrich the interpretations extracted from the CoMFA and CoMSIA contour maps, and to provide an in silico research method for the most favorable mode of interaction of an inhibitor within its receptor (CDK2). Conclusion: We have constructed and validated a quantitative 3D model of structure-activity relation-ships of pyrimidine-based benzothiazole derivatives as CDK2 inhibitors. This model allows us to identify the nature and position of the groups that enhance the activity, giving us directions to discover new, more powerful molecules in a limited time.

From Natural Compounds to Bioactive Molecules through NMR and In Silico Methodologies

2020 ◽  
Author(s):  
Simona De Vita ◽  
Stefania Terracciano ◽  
Ines Bruno ◽  
Maria Giovanna Chini
Keyword(s):  
In Silico ◽  
Natural Compounds ◽  
Bioactive Molecules

scholarly journals Bioactive molecules modelised by numerical simulation:molecules against Escherichia Coli

2014 ◽  
Vol 70 (a1) ◽  
pp. C1008-C1008
Author(s):  
Rita Kakou Yao ◽  
Jules Abodou Tenon ◽  
Akoun Abou
Keyword(s):  
Escherichia Coli ◽  
Biological Activity ◽  
In Silico ◽  
Biological Activities ◽  
Digital Simulation ◽  
Simulation Method ◽  
Bioactive Molecules ◽  
Structural Determination ◽  
Human Beings

The work exposed in this paper joins in the research of medecine by means of the modelling by digital simulation (method in silico). This method allows to plan the biological activities of new molecules and to design others more active than existing molecules against a given infection . The generated and validated models are used here in the research for molecules potentially more active against Escherichia coli which causes diarrheic infections at the human beings. Here, we report works the synthesis of our works of structural determination, of forecast of biological activity and conception of molecules bioactive again Eschericha coli.

scholarly journals INHIBITION OF α-AMYLASE AND α-GLUCOSIDASE BY (6RS)-22-HYDROXY-23,24,25,26,27-PENTANOR-VITAMIN-D3-6,19-SULFUR DIOXIDE-ADDUCT, MANOALIDE AND 5β-CHOLESTANE-3α,7α,12α,24,25,26-HEXOL ISOLATED FROM ACETONE EXTRACT OF HELIANTHUS ANNUUS L. SEEDS

2018 ◽  
Vol 10 (5) ◽  
pp. 39 ◽  
Author(s):  
Varsha V. Sonkamble ◽  
Nilesh S. Wagh ◽  
Laxmikant H. Kamble
Keyword(s):  
Helianthus Annuus ◽  
Vitamin D3 ◽  
In Silico ◽  
Binding Energies ◽  
Acetone Extract ◽  
Bioactive Molecules ◽  
Total Phenolic ◽  
Helianthus Annuus L ◽  
Kinetics Studies

Objective: This investigation includes characterization of phytochemicals from acetone extract of Helianthus annuus L. seeds responsible for α-amylase and α-glucosidase inhibition revealed from in vitro and in silico approaches.Methods: Seed extract was qualitatively and quantitatively analysed for the presence of bioactive molecules. In vitro α-amylase and α-glucosidase inhibition assays and kinetics studies for α-glucosidase were done. Thin layer chromatography (TLC) autography of extract was done to screen potent inhibitors and characterized by high-resolution liquid chromatography-mass spectrometry (HR LC-MS). Characterized molecules were further used for in silico studies.Results: Qualitative investigation reveals the presence of flavonoids, glycosides, alkaloids, terpenoids, and steroids. Quantitative analysis for total phenolic content and total flavonoid content of the extract was 0.1±0.005 mg/ml GAE and 0.025±0.003 mg/ml QE respectively. Percent inhibition of α-amylase and α-glucosidase ascertained in presence of extract was 60.42±0.6 and 83.22±0.18 at 0.01 mg while 36.24±0.81 and 37.67±0.15 at 0.005 mg of extracts for both enzymes respectively. Kinetics studies of α-glucosidase inhibition illustrated the non-competitive type of inhibition. TLC autography inhibition patterns were characterized by HR LC-MS. Characterized molecules on docking revealed (6RS)-22-hydroxy-23,24,25,26,27-pentanor-vitamin-D3-6,19-sulfurdioxide-adduct, manoalide and 5β-cholestane-3α,7α,12α,24,25,26-hexol as the best docked molecules with lowest binding energies of-12.5,-11 and-10.2 kcal/mol for α-amylase and-14.2,-11 and-11.2 kcal/mol for α-glucosidase respectively.Conclusion: Results clearly suggested that (6RS)-22-hydroxy-23,24,25,26,27-pentanor-vitamin-D3-6,19-sulfurdioxide-adduct, manoalide and 5β-cholestane-3α,7α,12α,24,25,26-hexol could be considered as lead molecules for the discovery of potent antidiabetic agents. 

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