scholarly journals A Potential Inhibition Process of Ricin Protein with the flavonoids Quercetin and Epigallocatechin Gallate. A Quantum-Chemical and Molecular Docking Study

Processes ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 1393
Author(s):  
Mayra Cristina Martínez-Ceniceros ◽  
Linda-Lucila Landeros-Martínez ◽  
Nora-Aydeé Sánchez-Bojorge ◽  
Fabiola Sandoval-Salas ◽  
Hilda Amelia Piñón-Castillo ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Quantum Chemical ◽  
Ricinus Communis ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Binding Energies ◽  
Molecular Structures ◽  
Molecular Docking Study ◽  
Inhibition Process

Castor bean (Ricinus Communis) oil has been reported as one of the most important bio-based fuels; however, high amounts of toxic solid residue are generated in the production. This toxicity is due to several molecules, ricin protein being the most studied compound. The inhibition of the ricin protein is essential for eliminating its toxicity. The objective of this study is to predict the possible inhibition process via the interactions between the ricin protein and the flavonoids quercetin (Q) and epigallocatechin gallate (EGCG). The molecular structures of the complexes formed between the ricin protein and flavonoids were studied using quantum-chemical and molecular docking calculations to analyze the type of interaction, active site of the protein, binding energies, and different conformations in the inhibition process. Different methodologies were applied for the molecular structure determination; the best approximation was obtained with B3LYP/6-31G (d,p) theoretical methodology. Mappings of electrostatic potential (MEP) and frontier molecular orbitals were used for the identification of the probable sites of interaction, which were confirmed by molecular docking. The adjustment and alignment of flavonoid groups before and after the interaction, and charge transfer parameters, showed that Q and EGCG act as electron donors inside of the active site in ricin.

Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

2020 ◽  
Vol 16 (7) ◽  
pp. 892-902 ◽  
Author(s):  
Aida Iraji ◽  
Mahsima Khoshneviszadeh ◽  
Pegah Bakhshizadeh ◽  
Najmeh Edraki ◽  
Mehdi Khoshneviszadeh
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Docking Study ◽  
Biological Evaluation ◽  
Primary Response ◽  
Ratio Method ◽  
Molecular Docking Study ◽  
Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

scholarly journals An Antioxidant Potential, Quantum-Chemical and Molecular Docking Study of the Major Chemical Constituents Present in the Leaves of Curatella americana Linn

2018 ◽  
Vol 11 (3) ◽  
pp. 72 ◽  
Author(s):  
Mayara Teles Fujishima ◽  
Nayara Silva ◽  
Ryan Ramos ◽  
Elenilze Batista Ferreira ◽  
Kelton Santos ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Xanthine Oxidase ◽  
Quantum Chemical ◽  
Binding Free Energy ◽  
Chemical Constituents ◽  
Docking Study ◽  
Antioxidant Potential ◽  
Molecular Docking Study ◽  
Hydroalcoholic Extract ◽  
Curatella Americana

Reactive oxygen species (ROS) are continuously generated in the normal biological systems, primarily by enzymes as xanthine oxidase (XO). The inappropriate scavenging or inhibition of ROS has been considered to be linked with aging, inflammatory disorders, and chronic diseases. Therefore, many plants and their products have been investigated as natural antioxidants for their potential use in preventive medicine. The leaves and bark extracts of Curatella americana Linn. were described in scientific research as anti-inflammatory, vasodilator, anti-ulcerogenic, and hypolipidemic effects. So, the aim of this study was to evaluate the antioxidant potentials of leaf hydroalcoholic extract from C. americana (HECA) through the scavenging DPPH assay and their main chemical constituents, evaluated by the following quantum chemical approaches (DFT B3LYP/6-31G**): Maps of Molecular Electrostatic Potential (MEP), Frontier Orbital’s (HOMO and LUMO) followed by multivariate analysis and molecular docking simulations with the xanthine oxidase enzyme. The hydroalcoholic extract showed significant antioxidant activity by free radical scavenging probably due to the great presence of flavonoids, which were grouped in the PCA and HCA analysis with the standard gallic acid. In the molecular docking study, the compounds studied presented the binding free energy (ΔG) values close each other, due to the similar interactions with amino acids residues at the activity site. The descriptors Gap and softness were important to characterize the molecules with antioxidant potential by capturing oxygen radicals.

scholarly journals Novel Group of AChE Reactivators—Synthesis, In Vitro Reactivation and Molecular Docking Study

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2291 ◽  
Author(s):  
David Malinak ◽  
Eugenie Nepovimova ◽  
Daniel Jun ◽  
Kamil Musilek ◽  
Kamil Kuca
Keyword(s):  
Molecular Docking ◽  
Molecular Modelling ◽  
Active Site ◽  
Molecular Design ◽  
Docking Study ◽  
The Novel ◽  
Molecular Docking Study ◽  
Causal Treatment ◽  
Modelling Study

The acetylcholinesterase (AChE) reactivators (e.g., obidoxime, asoxime) became an essential part of organophosphorus (OP) poisoning treatment, together with atropine and diazepam. They are referred to as a causal treatment of OP poisoning, because they are able to split the OP moiety from AChE active site and thus renew its function. In this approach, fifteen novel AChE reactivators were determined. Their molecular design originated from former K-oxime compounds K048 and K074 with remaining oxime part of the molecule and modified part with heteroarenium moiety. The novel compounds were prepared, evaluated in vitro on human AChE (HssAChE) inhibited by tabun, paraoxon, methylparaoxon or DFP and compared to commercial HssAChE reactivators (pralidoxime, methoxime, trimedoxime, obidoxime, asoxime) or previously prepared compounds (K048, K074, K075, K203). Some of presented oxime reactivators showed promising ability to reactivate HssAChE comparable or higher than the used standards. The molecular modelling study was performed with one compound that presented the ability to reactivate GA-inhibited HssAChE. The SAR features concerning the heteroarenium part of the reactivator’s molecule are described.

scholarly journals Identification of Compounds from Nigella Sativa as New Potential Inhibitors of 2019 Novel Coronasvirus (Covid-19): Molecular Docking Study.

2020 ◽  
Author(s):  
Salim Bouchentouf ◽  
Noureddine Missoum
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Nigella Sativa ◽  
Specific Treatment ◽  
Docking Study ◽  
Clinical Test ◽  
Molecular Docking Study ◽  
Great Opportunity ◽  
Drug Candidates ◽  
Energy Score

<p>The spread of the global COVID-19 pandemic, the lack of specific treatment and the urgent situation requires use of all resources to remedy this scourge. In the present study, using molecular docking, we identify new probable inhibitors of COVID-19 by molecules from <i>Nigella sativa L</i>, which is highly reputed healing herb in North African societies and both Islamic and Christian traditions. The discovery of the M<sup>pro</sup> protease structure in COVID-19 provides a great opportunity to identify potential drug candidates for treatment. Focusing on the main proteases in CoVs (3CL<sup>pro</sup>/M<sup>pro</sup>) (PDB ID 6LU7 and 2GTB); docking of compounds from <i>Nigella Sativa</i> and drugs under clinical test was performed using Molecular Operating Environment software (MOE). Nigelledine docked into 6LU7 active site gives energy complex about -6.29734373 Kcal/mol which is close to the energy score given by chloroquine (-6.2930522 Kcal/mol) and better than energy score given by hydroxychloroquine (-5.57386112 Kcal/mol) and favipiravir (-4.23310471 kcal/mol). Docking into 2GTB active site showed that α- Hederin gives energy score about-6.50204802 kcal/mol whcih is better energy score given by chloroquine (-6.20844936 kcal/mol), hydroxychloroquine (-5.51465893 kcal/mol)) and favipiravir (-4.12183571kcal/mol). Nigellidine and α- Hederin appeared to have the best potential to act as COVID-19 treatment. Further, researches are necessary to testify medicinal use of identified and to encourage preventive use of <i>Nigella Sativa </i>against coronavirus infection.</p>

scholarly journals MOLECULAR DOCKING STUDY TO IDENTIFY POTENTIAL INHIBITOR OF COVID-19 MAIN PROTEASE ENZYME: AN IN-SILICO APPROACH

2020 ◽  
Author(s):  
Anurag Agrawal ◽  
Nem Kumar Jain ◽  
Neeraj Kumar ◽  
Giriraj T Kulkarni
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Potential Threat ◽  
Discovery Studio ◽  
Chemical Structures ◽  
Potential Inhibitor ◽  
Protease Enzyme ◽  
Main Protease

This study belongs to identification of suitable COVID-19 inhibitors<br><div><br></div><div>Coronavirus became pandemic very soon and is a potential threat to human lives across the globe. No approved drug is currently available therefore an urgent need has been developed for any antiviral therapy for COVID-19. For the molecular docking study, ten herbal molecules have been included in the current study. The three-dimensional chemical structures of molecules were prepared through ChemSketch 2015 freeware. Molecular docking study was performed using AutoDock 4.2 simulator and Discovery studio 4.5 was employed to predict the active site of target enzyme. Result indicated that all-natural molecules found in the active site of enzyme after molecular docking. Oxyacanthine and Hypericin (-10.990 and -9.05 and kcal/mol respectively) have shown good binding efficacy among others but Oxyacanthine was the only natural product which made some of necessary interactions with residues in the enzyme require for target inhibition. Therefore Oxyacanthine may be considered to be potential inhibitor of main protease enzyme of virus but need to be explored for further drug development process. <br></div>

scholarly journals Isoniazid-Isatin Hydrazone Derivatives: Synthesis, Antitubercular Activity and Molecular Docking Studies

2021 ◽  
Vol 18 (21) ◽  
pp. 39
Author(s):  
Mardi Santoso ◽  
Muhammad Riza Ghulam Fahmi ◽  
Yehezkiel Steven Kurniawan ◽  
Taslim Ersam ◽  
Sri Fatmawati ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Mycobacterium Tuberculosis ◽  
Molecular Docking ◽  
Active Site ◽  
Antitubercular Activity ◽  
Docking Study ◽  
Positive Control ◽  
Tuberculosis H37rv ◽  
Molecular Docking Study

This study examined the synthesis of isoniazid-isatin hydrazone derivatives 5-7, followed by an investigation on the in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, and molecular docking. A yield of 81 - 92 % of these compounds was achieved, with structural characterization by spectroscopic methods (FTIR, NMR, HRMS). The in vitro antitubercular activity was evaluated against M. tuberculosis H37Rv, and the highest effect was observed in compound 7, with a minimum inhibitory concentration (MIC) of 0.017 mM, lower than rifampicin (MIC 0.048 mM), which served as the positive control. In addition, the molecular docking of 5-7 was performed to visualize the interaction of isoniazid-isatin hydrazone derivatives with the active site of InhA receptor, which was in agreement with the experimental data. The hydrogen bonding with Ser94 and pi-pi interaction with Phe41 and/or Phe97 on the InhA active site was pivotal for the antitubercular activity. HIGHLIGHTS Tuberculosis caused by Mycobacterium tuberculosis is one of the top ten leading causes of death globally The first and second lines of antituberculosis drugs are the prevalent treatment for this disease, but they show several drawbacks and are exacerbated by the occurrence of drug resistance The isoniazid-isatin hydrazone derivatives were designed through molecular hybridization and synthesized effectively and exhibited moderate to high activity against tuberculosis H37Rv Molecular docking study demonstrated that the hydrogen bonding with Ser94 and the pi-pi interaction with Phe41 and/or Phe97 are important for antitubercular activity GRAPHICAL ABSTRACT

scholarly journals Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study

2020 ◽  
Author(s):  
Trina Ekawati Tallei ◽  
Sefren Geiner Tumilaar ◽  
Nurdjannah Jane Niode ◽  
Fatimawali Fatimawali ◽  
Billy Johnson Kepel ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Bioactive Compounds ◽  
Binding Free Energy ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Ligand Complex ◽  
Main Protease ◽  
Glycoprotein Inhibitors

Since the outbreak of the COVID-19 (Coronavirus Disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease (Mpro) and Spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / &Delta;G). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

scholarly journals Molecular Docking Study and ADMET Profile: Manipulation of Angiotensin II Pathophysiology in COVID-19 by Potentilla Reptans Root Compounds

2021 ◽  
Author(s):  
Ayesheh Enayati ◽  
Hassan Mirzaei ◽  
Vahid Khori ◽  
Ali Jabbari ◽  
Aref Salehi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Angiotensin Ii ◽  
Active Site ◽  
Inflammatory Responses ◽  
Cardiac Injury ◽  
Ethyl Acetate Fraction ◽  
Docking Study ◽  
Angiotensin Ii Receptor ◽  
Molecular Docking Study ◽  
Potentilla Reptans

Abstract In the novel SARS-CoV-2 (COVID-19) as a global emergency event, the main reason of the cardiac injury from COVID-19 is angiotensin-converting enzyme 2 (ACE2) targeting in SARS-CoV-2 infection. The inhibition of ACE2 induces an increase in the angiotensin II (Ang II) and the angiotensin II receptor type 1 (AT1R) leading to impaired cardiac function or cardiac inflammatory responses. The ethyl acetate fraction of Potentilla reptans L. root can rescue heart dysfunction, oxidative stress, cardiac arrhythmias and apoptosis. Therefore, isolated components of P. reptans evaluated to identify natural anti-SARS-CoV-2 agents via molecular docking. In silico molecular docking study were carried out using the Auto Dock software on the isolated compounds of Potentilla reptans root. The protein targets of selective ACE and others obtained from Protein Data Bank (PDB). The best binding pose between amino acid residues involved in active site of the targets and compounds was discovered via molecular docking. Furthermore, ADMET properties of the compounds were evaluated. The triterpenoids of P. reptans showed more ACE inhibitory potential than catechin in both domains. They were selective on the nACE domain, especially compound 5. Also, the compound 5 & 6 had the highest binding affinity toward active site of nACE, cACE, AT1R, ACE2, and TNF-α receptors. Meanwhile, compound 3 showed more activity to inhibit TXA2. Drug likeness and ADMET analysis showed that the compounds passed the criteria of drug likeness and Lipinski rules. The current study depicted that P. reptans root showed cardioprotective effect in COVID-19 infection and manipulation of angiotensin II-induced side effects.

In silico Molecular Docking Study to Search New SGLT2 Inhibitor based on Dioxabicyclo[3.2.1] Octane Scaffold

2020 ◽  
Vol 16 (2) ◽  
pp. 145-154 ◽  
Author(s):  
Shubham Kumar ◽  
Gopal L. Khatik ◽  
Amit Mittal
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
In Silico ◽  
Promising Result ◽  
Sglt2 Inhibitor ◽  
Docking Study ◽  
Sglt2 Inhibitors ◽  
Molecular Structures ◽  
Molecular Docking Study ◽  
Us Fda

Background: Diabetes is a leading cause of high mortality rate in the world. Recently, SGLT2 inhibitors showed the promising result to treat diabetes and therefore several molecules are approved by the US FDA. Objective: SGLT2 inhibitors were designed based on dioxabicyclo[3.2.1] octane with the aim to search new lead molecule. Methods: The molecular structures were drawn in ChemBiodraw ultra and molecular docking study was performed by AutoDock Vina 1.5.6 software. The LogP and toxicity were predicted online using AlogP and Lazar in-silico respectively. Results: Among all the designed molecules, SK306 showed the maximum binding affinity against the 3dh4 SGLT2 protein of Vibrio parahaemolyticus. LogP values were also calculated in order to determine the lipophilic property of the best binding molecules which show LogP 2.82-3.79 in the range for good absorption and elimination, also predicted to be non-toxic. Conclusion: SGLT2 inhibitors were designed based on the dioxabicyclo [3.2.1] octane resulting in a new lead molecule with high binding affinity; also these molecules were predicted to be noncarcinogenic with low LogP.

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