scholarly journals MODULATORY ANTI- DIARRHEAL EFFECTS OF ASCORBIC ACID IN SWISS ALBINO MICE

2021 ◽  
Vol 18 (1) ◽  
pp. 9-17
Keyword(s):  
Ascorbic Acid ◽  
Adrenergic Receptor ◽  
Castor Oil ◽  
Docking Study ◽  
Binding Affinities ◽  
Molecular Docking Study ◽  
Receptor Blocking ◽  
Swiss Mice ◽  
Mixed Groups ◽  
The Impact

Ascorbic acid (AA) has been reported for the management of diarrhea. The anti-diarrheal potential and modulatory activities of AA on some commonly used anti-diarrheal drugs were investigated. For this purpose, the activities of AA on castor oil-induced diarrhea in Swiss mice were examined. As standard anti-diarrheal agents, we used prazosin, propranolol, loperamide, and nifedipine with or without AA. The results revealed that AA at 25 mg/kg (i.p.) and all other standard drugs exhibited significant (p < 0.05) diarrheal attenuating activities in mice. However, the impact was more pronounced in the loperamide and propranolol groups. AA administrated with prazosin and propranolol had a higher rate of latent periods and a lower rate of diarrheic secretion during the study period (4 h) than that of the other single or mixed groups. Furthermore, a molecular docking study illustrated that AA displayed good binding affinities with (α1) (–5.2 Kcal/mol), α2b (–5.4 Kcal/mol), α2c (-5.6 Kcal/mol), β1(–5.3 Kcal/mol) and β2(–6.4 Kcal/mol) adrenoceptors. Of note, AA exerted a significant anti-diarrheal effect and it was seen to modulate the anti-diarrheal effects of α- and β-adrenergic receptor blocking agents in Swiss mice.

Novel 1,2-thiazine-pyridine hybrid: Design, synthesis, antioxidant activity and molecular docking study

2022 ◽  
Vol 19 ◽  
Author(s):  
Rania B. Bakr ◽  
Nadia A.A. Elkanzi
Keyword(s):  
Antioxidant Activity ◽  
Ascorbic Acid ◽  
Biological Activities ◽  
Radical Scavenging ◽  
Reducing Power ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Sod Activity ◽  
Design Synthesis ◽  
In Silico Docking

Background & objectives: 1,2-thiazine and pyridine heterocycles drew much attention due to their biological activities including antioxidant activity. Based upon fragment based drug design, novel pyrido[1,2]thiazines 9a-c, thiazolidinopyrido[1,2]thiazines 10a-c and azetidinopyrido[1,2]thiazines 11a-c were designed and prepared. Methods: These novel derivatives 9a-c, 10a-c and 11a-c were subjected to screening for their antioxidant activity via various assays as DPPH radical scavenging potential, reducing power assay and metal chelating potential. Results: All the assayed derivatives exhibited excellent antioxidant potential and the tested compounds 9a, 9b, 10a, 10b, 11a and 11b exhibited higher DPPH scavenging potential (EC50 = 32.7, 53, 36.1, 60, 40.6 and 67 µM, respectively) than ascorbic acid (EC50 = 86.58 µM). While targets 9a, 10a and 11a (RP50 = 52.19, 59.16 and 52.25 µM, respectively) exhibited better reducing power than the ascorbic acid (RP50 = 84.66 µM). Computational analysis had been utilized to prophesy the bioactivity and molecular properties of the target compounds. Conclusion: To predict the binding manner of the novel derivatives as antioxidants, in-silico docking study had been performed to all the newly prepared compounds inside superoxide dismutase (SOD) and catalase (CAT) active site. The most active antioxidant candidate 9a (EC50 = 32.7 µM, RP50 = 52.19 µM) displayed excellent binding with Lys134 amino acid residing at Cu-Zn loop of SOD with binding energy score = -7.54 Kcal/mol thereby increase SOD activity and decrease reactive oxygen species.

scholarly journals (S)-5-Methylmellein Isolated from an Endogenous Lichen Fungus Rosellinia corticium as a Potent Inhibitor of Human Monoamine Oxidase A

Processes ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 166
Author(s):  
Geum-Seok Jeong ◽  
Eun-Young Lee ◽  
Myung-Gyun Kang ◽  
Sang-Jip Nam ◽  
Daeui Park ◽  
...  
Keyword(s):  
Potent Inhibitor ◽  
Docking Study ◽  
Competitive Inhibitor ◽  
Monoamine Oxidase A ◽  
Pharmacokinetic Analysis ◽  
Binding Affinities ◽  
Molecular Docking Study ◽  
Ic50 Value ◽  
Brain Barrier Permeability ◽  
Lichen Fungus

In this study, the inhibitory activities against human monoamine oxidases (hMAOs) were evaluated using a library of 195 endogenous lichen fungi from Ukraine. Among them, the extract ELF68 of the endogenous fungus Rosellinia corticium from the lichen Pseudevernia furfuracea (L.) Zopf. exhibited the strongest inhibitory activity against hMAO-A. Using the activity-guided method, (S)-5-methylmellein (5MM) was isolated from the extract and had an IC50 value of 5.31 µM for hMAO-A with a lower potency for hMAO-B (IC50 = 9.15 µM). Compound 5MM also moderately inhibited acetylcholinesterase (IC50 = 27.07 µM) but very weakly inhibited butyrylcholinesterase and β-secretase. Compound 5MM had a Ki value of 2.45 μM and was a reversible competitive inhibitor of hMAO-A. A molecular docking study predicted that (S)-5MM showed higher binding affinity for hMAO-A (−6.8 kcal/mol) than hMAO-B (−6.4 kcal/mol). Its isomer, (R)-5MM, exhibited lower binding affinities for hMAO-A (−6.6 kcal/mol) and hMAO-B (−5.2 kcal/mol), compared to (S)-5MM. The S-form interacted with hMAO-A through hydrogen bonding with the Phe208 residue (distance: 1.972 Å), while the R-form interacted with the Asn181 residue (2.375 Å). The results of an in silico pharmacokinetic analysis indicated that 5MM did not violate Lipinski’s five rules and showed high gastrointestinal absorption and blood–brain barrier permeability. These results suggest that 5MM can be considered a candidate in the treatment of neuropsychiatric disorders, such as depression and cardiovascular disease.

scholarly journals Tripeptides from Allium subhirsitum L. extracts: Pharmacokinetics properties, toxicity prediction and in silico study against SARS-CoV-2 enzymes and pro-inflammatory proteins

2022 ◽  
Vol 67 (4) ◽  
pp. 143-162
Author(s):  
Mejdi Snoussi ◽  
Emira Noumi ◽  
Amor Mosbah ◽  
Alaeddine Redissi ◽  
Mohd Saeed ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Docking Study ◽  
Strong Interactions ◽  
Binding Affinities ◽  
Toxicity Prediction ◽  
Molecular Docking Study ◽  
Multiplication Cycle ◽  
In Silico Study ◽  
Antiviral Activities ◽  
Inflammatory Proteins

Developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities is urgently needed to combat emerging human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since no available clinically antiviral drugs have been approved to eradicate COVID-19 as of the writing of this report, this study aimed to investigate bioactive short peptides from Allium subhirsutum L. (Hairy garlic) extracts identified through HR-LC/MS analysis that could potentially hinder the multiplication cycle of SARS-CoV-2 via molecular docking study. The obtained promising results showed that the peptides (Asn-Asn-Asn) possess the highest binding affinities of -8.4 kcal/mol against S protein, (His-Phe-Gln) of -9.8 kcal/mol and (Gln-His-Phe) of -9.7 kcal/mol towards hACE2, (Thr-Leu-Trp) of -10.3 kcal/mol and (Gln-Phe-Tyr) of -9.8 kcal/mol against furin. Additionally, the identified peptides show strong interactions with the targeted and pro-inflammatory ranging from -8.1 to -10.5 kcal/mol for NF−κB-inducing kinase (NIK), from -8.2 to -10 kcal/mol for phospholipase A2 (PLA2), from -8.0 to -10.7 kcal/mol for interleukin-1 receptor-associated kinase 4 (IRAK-4), and from -8.6 to -11.6 kcal/mol for the cyclooxygenase 2 (COX2) with Gln-Phe-Tyr model seems to be the most prominent. Results from pharmacophore, drug-likeness and ADMET prediction analyses clearly evidenced the usability of the peptides to be developed as an effective drug, beneficial for COVID-19 treatment.

scholarly journals Anticonvulsant Activity, Molecular Modeling and Synthesis of Spirooxindole-4H-Pyran Derivatives using a Novel Reusable Organocatalyst

2021 ◽  
Author(s):  
Leila Emami ◽  
Leila Moezi ◽  
Leila Amiri-Zirtol ◽  
Fatemeh Pirsalami ◽  
Masoumeh Divar ◽  
...  
Keyword(s):  
Anticonvulsant Activity ◽  
Binding Free Energy ◽  
Docking Study ◽  
Positive Control ◽  
High Catalytic Activity ◽  
Binding Affinities ◽  
Molecular Docking Study ◽  
Gaba A ◽  
Physico Chemical ◽  
Ptz Test

Abstract Fifteen derivatives of spirooxindole-4H-pyran (A1-A15) were subjected to evaluate through intravenous infusion of pentylenetetrazole (PTZ) induced epilepsy mouse models. Four doses of the compounds (20, 40, 60, 80 mg/kg) were tested in comparison to diazepam as positive control. The resulted revealed that compounds A3 and A12 were the most active compounds and indicated significant anticonvulsant activity in the PTZ test. The tested compounds were prepared via a multicomponent reaction using graphene oxide (GO) based on the 1-(2-aminoethyl) piperazine as a novel heterogeneous organocatalyst. The prepared catalyst (GO-A.P.) was characterized using some diverse microscopic and spectroscopic procedures as well. The results showed high catalytic activity of the catalyst in the synthesis of spirooxindole-4H-pyran derivatives. The GO-A.P. catalyst was reusable at least for 5 times with no significant decrease in its catalytic action. In silico assessment of physico chemical activity of all compounds also were done which represented appropriate properties. Finally, molecular docking study was performed to achieve their binding affinities as γ-aminobutyric acid-A (GABA‐A) receptor agonists as a plausible mechanism of their anticonvulsant action. Binding free energy values of the compounds represented strongly matched with biological activity.

Novel Guanosine Derivatives as Anti-HCV NS5b Polymerase: A QSAR and Molecular Docking Study

2019 ◽  
Vol 15 (2) ◽  
pp. 130-137 ◽  
Author(s):  
Abdo A. Elfiky
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Active Site ◽  
Docking Study ◽  
Binding Affinities ◽  
Molecular Docking Study ◽  
Docking Calculations ◽  
Quantitative Structure Activity Relationships ◽  
Hcv Ns5b ◽  
Ns5b Polymerase

Background: IDX-184 is a guanosine derivative having a potent inhibitory performance against HCV NS5b polymerase. Objective: To test three different groups of 2'C - modified analogues of guanosine nucleotide against HCV polymerase. Method: Using combined Quantitative Structure-Activity Relationships (QSAR) and molecular docking, the suggested compounds are studied. Results: Examining the docked structures of the compounds with experimentally solved NS5b structure (PDB ID: 2XI3) revealed that most of the compounds have the same mode of interaction as that of guanosine nucleotide and hence, NS5b inhibition is possible. Conclusion: It is revealed that sixteen modifications have a better binding affinity to NS5b compared to guanosine. In addition, seven more compounds are better in NS5b binding compared to the approved drug, sofosbuvir, and the compound under clinical trials, IDX-184. Hence, these compounds could be potent HCV NS5b inhibitors. Summary Points: Novel guanosine modifications were introduced in silico and optimized using QM. QSAR and docking calculations are performed to test the binding affinity of the compounds to HCV NS5b active site. Comparison between the binding affinities and the mode of interactions of the compounds and both GTP and IDX-184 is performed. Structural mining to quantify the mode of binding of the compounds to NS5b active site pocket.

scholarly journals Molecular Docking Study of Several Antiviral Drugs to Defeat Covid-19

2020 ◽  
Vol 19 (3) ◽  
pp. 37-46
Author(s):  
Jasdev S. Tuteja ◽  
Priti Patidar ◽  
Shilpa E. Mathew ◽  
Anil Prajapati
Keyword(s):  
Molecular Docking ◽  
Severe Acute Respiratory Syndrome ◽  
Active Drug ◽  
Data Bank ◽  
Docking Study ◽  
Antiviral Drugs ◽  
Binding Affinities ◽  
Molecular Docking Study ◽  
Molegro Virtual Docker ◽  
Docking Approach

Corona virus is one of the significant pathogens that destructs the human respiratory functioning. Deaths and casualties caused by coronaviruses (CoVs) include the severe acute respiratory syndrome (SARS)-CoV and the Middle East respiratory syndrome (MERS)-CoV. The aim of the work was to compare several antiviral drugs and find out which is the most active drug that might be used in treatment for COVID -19. In this study Molecular Docking approach was used to determine the binding affinities of 62 antiviral molecules. The study was carried out using Molegro Virtual Docker 6.0 with PDB 2GTB procured from RCSB Protein Data Bank. Simeprevir and Telaprevir were discovered to be most potent having high MolDock and Rerank scores of -225.158, -78.4383 and -209.467, -136.155 respectively. Further studies may be conducted to design more potent analogue and defeat COVID-19.

scholarly journals Azole-acridine hybrids as potential enzymatic inhibitors of coronavirus-2 main protease and RNA polymerase by molecular modeling strategy

2020 ◽  
Author(s):  
Charles K. Rono ◽  
Banothile C.E. Makhubela
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Docking Study ◽  
Living Cells ◽  
Binding Energies ◽  
Binding Affinities ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Current Outbreak ◽  
Modeling Strategy

Abstract SARS-CoV-2 has been identified as the cause of the current outbreak of coronavirus disease (COVID-19). As part of the efforts to develop potential drugs with promise for clinical use, a molecular docking study on azole (triazole and pyrazole) based molecules on the main protease Mpro and RNA polymerase as possible inhibitors that could be elected for further experimental bioassays. Autodock has been employed to identify azole derivatives 1-6 preferred conformations in the active site of the enzyme and to estimate their binding affinities to the protease and RNA polymerase targets. From the molecular docking strategy, these new azole compounds though nonpeptides in nature display possible inhibition of Mpro activity with comparable affinities (-4.7 kcal/mol to -6.5 kcal/mol) to the recently reported peptide-like inhibitors such as α-ketoamide inhibitor 13b (-5.0 k/cal/mol). They also exhibit improved binding affinities to RNA polymerase (-6.3 to -7.1 kcal/mol) comparable to remdesivir (-6.6 kcal/mol). Based on the observed binding energies, these compounds may possess anti-coronavirus bioactivity through inhibition of the virus main protease as well as RNA polymerase activities in living cells.

scholarly journals Molecular Docking Evaluation of Syzygium aromaticum Isolated Compounds Against Exo-β-(1,3)-glucanases of Candida albicans

2021 ◽  
pp. 34-44
Author(s):  
Mohammed H. F. Shalayel ◽  
Ghassab M. Al-Mazaideh ◽  
Farhan Khashim Al Swailmi ◽  
Saleem Aladaileh ◽  
Saada Nour ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Molecular Docking ◽  
Active Site ◽  
Inhibitory Activity ◽  
Docking Study ◽  
Syzygium Aromaticum ◽  
Binding Affinities ◽  
Molecular Docking Study ◽  
Pubchem Database

Seventeen compounds from Syzygium aromaticum are selected for exo-β-(1,3)-glucanases inhibitory activity by using molecular docking study. The compounds are uploaded from the PubChem database and molecular docking with AutoDock 1.5.6 tools is carried out. The molecular docking scores indicate that stigmasterol and campesterol are of the highest potentials, and approximately have similar binding affinities with Candida albicans' active site (3N9K, 3O6A). The hydroxyl moiety has played an important role in the antifungal potentiality of all studied compounds.

scholarly journals Azole-acridine hybrids as potential enzymatic inhibitors of coronavirus-2 main protease and RNA polymerase by molecular modeling strategy

2020 ◽  
Author(s):  
Charles K. Rono ◽  
Banothile C.E. Makhubela
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Docking Study ◽  
Living Cells ◽  
Binding Energies ◽  
Binding Affinities ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Current Outbreak ◽  
Modeling Strategy

Abstract SARS-CoV-2 has been identified as the cause of the current outbreak of coronavirus disease (COVID-19). As part of the efforts to develop potential drugs with promise for clinical use, a molecular docking study on azole (triazole and pyrazole) based molecules on the main protease Mpro and RNA polymerase was conducted, as possible inhibitors that could be elected for further experimental bioassays. Autodock has been employed to identify azole derivatives 1-6 preferred conformations in the active site of the enzyme and to estimate their binding affinities to the protease and RNA polymerase targets. From the molecular docking strategy, these new azole compounds though nonpeptides in nature display possible inhibition of Mpro activity with comparable affinities (-4.7 kcal/mol to -6.5 kcal/mol) to the recently reported peptide-like inhibitors such as α-ketoamide inhibitor 13b (-5.0 k/cal/mol). They also exhibit improved binding affinities to RNA polymerase (-6.3 to -7.1 kcal/mol) comparable to remdesivir (-6.6 kcal/mol). Based on the observed binding energies, these compounds may possess anti-coronavirus bioactivity through inhibition of the virus main protease as well as RNA polymerase activities in living cells.

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