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 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.

scholarly journals In silico Study of the Interactions between Schiff Base Polyphenols and HPV 16 E6/E6AP/p53 complex

2021 ◽  
pp. 3973-3980
Author(s):  
Jeremiah I. Ogah ◽  
Olatunji M. Kolawole ◽  
Steven O. Oguntoye ◽  
Muhammed Mustapha Suleiman
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
In Silico ◽  
In Silico Analysis ◽  
Docking Study ◽  
Hydrogen Atoms ◽  
Molecular Docking Study ◽  
Hpv 16 ◽  
In Silico Study

The rise in the incidence of cervical cancer globally has accentuate attention to the potential role of polyphenols as anticancer agents. Different studies have demonstrated the role of some polyphenols in altering Human Papillomavirus (HPV) carcinogenesis. Thus, this study was aimed at establishing the potentials of Schiff-based polyphenols from imesatin and satin as anticancer agents through in silico analysis. The polyphenols were synthesized and characterized using elemental analyses, spectroscopic analyses, UV-visible, Infrared, and Nuclear Magnetic Resonance (1H NMR and 13C, NMR). Molecular docking study of the polyphenols was carried out using Auto Dock Vina. The oncogenic E6 protein structure of HPV 16 was obtained from the protein bank (ID: 4XR8). The E6 proteins were prepared using AutoDock tools. Water molecules were removed from the protein molecules while hydrogen atoms were added. Also, the structures of Curcumin and Isomericitrin were obtained from PubChem. Results showed that three different Schiff based polyphenols were obtained from the synthesis; 3-(2’,4’-dimethoxy benzylidene hydrazono) indoline-2-one (DMBH), 3-(2’-hydroxy-4’-methoxy benzylidene hydrazono) indoline-2-one (HMBD), and 3-((4-4’-((2’’, 4’’-dimethoxy benzylidene amino) benzyl)phenyl)imino) indoline-2-one (DMBP). Higher ability of the docked polyphenols to bind to the E6/E6AP/p53 complex when compared to Curcumin was revealed. Also, results showed that the binding energy of Curcumin and Isomericitrin were -7.1kcal/mol and -8.4kcal/mol respectively while that of the polyphenols ranged from -7.4kcal/mol to -7.9kcal/mol. The molecular docking results of the polyphenols used in this study further confirm their potentials as strong anti-cancer agents.

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 Natural products as anti-COVID-19 agents: An in silico study

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Chandan Sarkar ◽  
Sarmin Jamaddar ◽  
Milon Mondal ◽  
Abul Bashar Ripon Khalipha ◽  
Muhammad Torequl Islam ◽  
...  
Keyword(s):  
In Silico ◽  
Rna Virus ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Docking Study ◽  
Asiatic Acid ◽  
Molecular Docking Study ◽  
Viral Protease ◽  
In Silico Study ◽  
To Come

Background: The coronavirus disease 2019 (COVID-19) is a life threatening viral infection caused by a positivestrand RNA virus belonging to Coronaviridae family called severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). This virus has infected millions of peoples, and caused hundreds of thousands of deaths around the world. Unfortunately, to date, there is no specific cure for SARS-CoV-2 infection, although researchers are working tirelessly to come up with a drug against this virus. Recently, the main viral protease has been discovered, and is regarded as an appropriate target for antiviral agents in the search for treatment of SARS-CoV-2 infection, due to its role in polyproteins processing during coronavirus replication. Methodology: This investigation (an in silico study) explores the effectiveness of 16 natural compounds from a literature survey against the protease of SARS-CoV-2 in an attempt to identify a promising antiviral agent through a molecular docking study. Results: Among the 16 compounds studied, apigenin, alpha-hederin, and asiatic acid exhibited significant docking performance and interacted with several amino acid residues of the main protease of SARS-CoV-2. Conclusion: In summary, apigenin, alpha-hederin, and asiatic acid protease inhibitors may be effective potential antiviral agents against the main viral protease (Mpro) to combat SARS-CoV-2.

scholarly journals Design and In Silico Study of the Novel Small Molecular MDM2 Inhibitors

2020 ◽  
Vol 11 (1) ◽  
pp. 8052-8064
Keyword(s):  
Protein Interaction ◽  
In Silico ◽  
P53 Protein ◽  
Docking Study ◽  
Rational Approach ◽  
The Novel ◽  
Molecular Docking Study ◽  
Protein Protein Interaction ◽  
In Silico Study ◽  
Cancer Agent

Protein-protein Interaction (PPIs) plays a central role in many diseased conditions. Therefore to target and to modulate PPIs is an efficient approach for the disease treatment. Cancer is also arising because of Protein-protein interaction. In cancer, the tumor suppressor p53 protein got inhibited by the MDM2 protein. p53 protein regulates the cell cycle and apoptosis. Interaction between the p53-MDM2 proteins is responsible for the inhibition of the p53 function. By this interaction, MDM2 degrades and inhibits the p53 protein. Hence, to target and inhibit the p53-MDM2 interaction for the treatment of cancer is the rational approach. By targeting this interaction with the drugs, we can selectively kill the cancer cells over the normal cells. Recently, p53-MDM2 interaction inhibitor drugs have been reported by many researchers and pharmaceutical companies. And several drugs entered into the clinical trials. In this study, a novel 1,2,4-triazole based molecules were designed as MDM2 inhibitors and performed their in-silico study. We designed the novel compound 01 and Lead 1a. In this work, In silico study of the Lead 1a and reference compounds (Nutlin 3a, RG7112) was carried out. The molecular docking study of the Novel 1,2,4-triazole based lead 1a and reference compounds was carried out. The docking score of the Lead 1a found to be better than Nutlin 3a and close to RG7112. The various possible conformations and binding affinity values were also determined by the docking study. These results indicate the Lead 1a as a potential MDM2 inhibitor and anti-cancer agent.

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.

Synthesis, antineoplastic activity and in silico studies of (S)-N-(1-hydroxy-3-methylbutan-2-yl)-3-(p-tolyl)-1,2,4-oxadiazole-5-carboxamide

2021 ◽  
Vol 25 (7) ◽  
pp. 167-176
Author(s):  
Cláudia Laís Araújo Almeida Santos ◽  
Jonh Anderson Macêdo Santos ◽  
Rodrigo Ribeiro Alves Caiana ◽  
Silvia Maria Souza ◽  
Jucleiton José Rufino Freitas ◽  
...  
Keyword(s):  
In Silico ◽  
Low Cost ◽  
Docking Study ◽  
New Drugs ◽  
Molecular Docking Study ◽  
Traditional Medicines ◽  
In Silico Studies ◽  
In Silico Study ◽  
Pharmacokinetic Properties ◽  
Low Toxicity

The development of chemotherapy agents without side effects is a major challenge, since traditional medicines usually have undesirable properties such as high toxicity, resistance and low bioavailability. In this sense, computational methods play a crucial role in the discovery and optimization of new drugs, as they combine speed and efficiency with low cost. The 1,2,4-oxadiazoles are one of the main classes of heterocyclics due to their numerous biological applications. In this work, we report the synthesis, antineoplastic evaluation and in silico study of a new 1,2,4-oxadiazole. The (S)-N-(1-hydroxy-3-methylbutan-2-yl)-3-(p-toluyl)-1,2,4-oxadiazole-5-carboxamide was obtained after two reaction steps in excellent yield. Although it has shown low activity in relation to the MCF-7, HCT116 and HL60 tumor cell lines, the molecular docking study indicates that this compound acts in the colchicine site and can inhibit tubulin polymerization. From the calculation of pharmacokinetic properties by the SwissADME and Osiris Property Explorer programs, it is possible to infer that the compound meets the Lipinski rules presenting good oral bioavailability and low toxicity.

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.

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..

Sign in / Sign up

Export Citation Format

Share Document