•Synthesis by reflux method a novel symmetrical azine Schiff base "IVa".•The target compounds structures were ascertained using X-ray analysis, FT-IR spectral data, 1H NMR, 13C NMR and UV–Vis ...spectral information.•DFT/B3LYP/6–31 G (d,p) level theory was used to conduct computational research on the produced molecules.•The tested compound showed promising DPPH radical scavenging activity with a 68 μmol/mL concentration.•The in silico molecular docking and molecular dynamics study reveals stabilizing interactions between the azine and 2B7F receptor.
Isovanillin azine, a symmetrical azine easily synthesized by reaction of 3-hydroxy-4-methoxybenzaldehyde (isovanillin) with hydrazine hydrate, was identified as a potential inhibitor of the Human T-cell Leukemia Virus type 1 (HTLV-1) protease (2B7F). The compound was characterized using FT-IR, UV-VIS, 1H NMR, and 13C NMR spectroscopic techniques, as well as by single-crystal X-ray diffraction at 100 K. Additionally, calculations were conducted on the FMOs, particularly the HOMO-LUMO, to determine the forbidden energy gap and assess the compound's properties. To properly and accurately evaluate the effectiveness of our product as an anticancer drug, we investigated its interactions with 2B7F through molecular docking experiment and MD simulation. The results indicate that isovanillin azine has the potential to effectively inhibit 2B7F, laying the groundwork for the development of targeted treatments for HTLV-1-related disorders.
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•The two organic inhibitors studied act as efficient corrosion inhibitors.•Nitrogen and oxygen heteroatoms are the most basic active site.•Quantum chemical parameters were in good ...correlation with experimental results.•MD simulation showed that the two inhibitors were adsorbed on parallel position to Fe (110).•Adsorption of both inhibitors on mild steel surface obeys Langmuir’s isotherm.
In this study, two organic compounds were synthesized: N-(2E)-3-phenylprop-2-en-1-ylaniline (PPA-1) and 4-{(2E)-3-phenylprop-2-en-1-ylamino}phenol (PPAP-2). Their structures were confirmed by DRIFT, 1H and 13C NMR spectroscopy analyses. The two organic molecules were inspected as corrosion inhibitors of mild steel in HCl medium. The experimental studies such as electrochemical impedance spectroscopy, potentiodynamic polarization and surface analysis were conducted in order to prove the corrosion inhibition of these molecules and to confirm the presence of the organic film on the mild steel surface. Furthermore, theoretical studies by density functional theory and molecular dynamic simulation were used to corroborate the electrochemical results and to establish the adsorption mechanism and the orientation of the two organic molecules at the interface mild steel-aggressive solution. Langmuir adsorption isotherm model was used to explain the adsorption of the two molecules in HCl solution. Mulliken charges, Fukui functions, proton affinity and gas-phase basicity indicate that the nitrogen and oxygen heteroatoms are the most basic active site. Molecular dynamics simulation showed that the two inhibitors were adsorbed almost parallel on the Fe (110) surface attesting the high inhibition performances.
Structural rearrangements taking place during relaxation and crystal nucleation in lithium-disilicate (LS2) glass have been investigated by a comprehensive set of solid-state nuclear magnetic ...resonance (NMR) experiments, supported by molecular dynamics (MD) simulations. Samples were subjected to heat treatments at 435 °C, i.e., 20 K below the laboratory glass transition temperature (Tg). Raman and NMR data indicate that under these conditions both relaxation and nucleation occur without detectable changes in the network former unit distribution of the glassy silicon-oxide network. Instead, relaxation of the frozen supercooled melt and nucleation of LS2 crystals occur principally in terms of a changing lithium local environment: 7Li spin-echo decay NMR indicates average Li-Li distances, characterized by homonuclear dipolar second-moment measurements, are reduced after very short heat treatments and approach those found in the isochemical crystal. This finding is supported by molecular dynamics (MD) simulations predicting a dependence of the Li+ ion distribution on the melt-cooling rate. In addition, the structural reorganization also impacts the distribution of electric field gradients as detected by 7Li satellite transition NMR spectroscopy. Finally, crystal nucleation becomes most evident by the appearance of minor amounts of sharp 29Si MAS resonances and a significant change in the 7Li NMR satellite transitions, as visualized by difference spectroscopy. This study defines a new NMR strategy, generally applicable for investigating the structural relaxation process accompanying the internal crystallization of ion-conducting frozen supercooled melts containing suitable NMR active nuclear probes (7Li, 23Na, 133Cs, etc.).
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•Double azomethine functional Schiff bases protect mild steel in 1 mol L−1 HCl medium.•Inhibition efficiency obtained from EIS corroborates with the weight loss results.•Effect of ...molecular flexibility on its inhibition efficiency is described.•FESEM, AFM and contact angle measurements affirmed the adsorption of inhibitors on metal surface.•DFT, DFTB and MD simulation studies are in agreement with the experimental findings.
Two hitherto unexplored double condensed Schiff bases, namely, 4-(4-((Pyridin-2-yl)methyleneamino)phenoxy)-N-((pyridin-2-yl)methylene)benzenamine (PMB) and 4-(4-(4-((Pyridin-2-yl)methyleneamino)phenoxy)phenoxy)-N-((pyridin-2-yl)methylene)benzenamine (PPMB) were synthesized and their corrosion inhibitive performances on mild steel have been investigated in 1 mol L−1 HCl medium by gravimetric and electrochemical measurements. Field emission scanning electron microscopy, energy dispersive X-ray spectroscopy and atomic force microscopy affirmed the formation of protective films on mild steel surfaces. Contact angle measurement revealed the hydrophobic nature of surface modified by the inhibitor molecules applied in the corrosive solution. The influence of molecular configuration in corrosion inhibition behaviour of inhibitors has been explored by DFT, DFTB calculation and MD simulation.
•Morellic acid isolated from Garcinia wightii.•Experimental spectroscopic characterization compared with theoretical DFT/TD-DFT results.•NBO and HOMO-LUMO analysis reveal resonance-assisted hydrogen ...bonding and intramolecular hydrogen bonding interactions.•Molecular docking and molecular dynamics simulation studies revealed the potential of morellic acid as a tuberculosis treatment candidate.
The current study elaborates on experimental and simulated methods using density functional theory (DFT) to analyze the structure, electronic characteristics, and vibrational features of morellic acid, an isolate from Garcinia wightii. The in-depth examination of the stabilized structure indicates that the compound achieves equilibrium through conjugative, hyperconjugative, resonance-assisted hydrogen bonding (RAHB), and intramolecular hydrogen bonding (IHB) interactions, resulting in a well-supported conformation. The vibrational spectra were recorded, and the wavenumbers were comprehensively assigned using Potential Energy Distribution with a scaled quantum mechanical force field. Natural bond orbital (NBO) studies were utilized to calculate donor and acceptor bond interaction energy and electron densities. The TD-DFT computations were performed in solvent (chloroform) and gaseous phase, which agreed with the experimental values. Molecular electrostatic potential (MEP), reduced density gradient (RDG), electron localized function (ELF), and localized orbital locator (LOL) of the molecule were also analyzed. The molecular docking studies revealed that the compound holds great promise as a drug candidate for tuberculosis treatment, with the most thermodynamically stable binding score of -11.542 kcal/mol with 4BFS (protein of Mycobacterium tuberculosis PanK). The molecular dynamics (MD) simulation studies examined the stability and hydrogen bonding system of the ligand-protein complex formed between the molecule and the essential target protein for 100 ns. The findings revealed that the complex remained stable with minimal fluctuations throughout the simulation, suggesting that the molecule may prevent tuberculosis and be used as a treatment candidate.
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Coronavirus Disease (COVID-19) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The virus was named Severe Acute Respiratory Syndrome ...Coronavirus 2 (SARS-CoV-2), (Coronavirus Disease 2019). Currently, there is no specific drug for the therapy of COVID-19. So, there is a need to develop or find out the new drug from the existing to cure the COVID-19. Identification of a potent inhibitor of Methyltransferase, Endoribonuclease, Phosphatase and Main Protease enzymes of SARS CoV-2 by coumarin derivatives using insilico approach. The in silico studies were performed on maestro 12.0 software (Schrodinger LLC 2019, USA). Two thousand seven hundred fifty-five biologically active coumarin derivative was docked with above receptor proteins of SARS CoV-2. The molecular dynamic simulation of the top one ligand of respected proteins was performed. Top five ligands of each protein were taken for study. Coumarin derivatives actively interact with taken receptors and showed good docking results for Methyltransferase, Endoribonuclease, Phosphatase and Main Protease and top five compounds of each have docking score from -9.00 to -7.97, -8.42 to -6.80, -8.63 to -7.48 and -7.30 to -6.01 kcal/mol, respectively. The docked compounds were showed RMSD and binding stability of simulated ligands are show the potency of ligands against the SARS CoV-2. Our study provides information on drugs that may be a potent inhibitor of COVID-19 infection. Drug repurposing of the available drugs would be great help in the treatment of COVID-19 infection. The combination therapy of the finding may improve inhibitory activity.
Communicated by Ramaswamy H. Sarma
Highlights
Coronavirus Disease (COVID-19) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
In silico virtual screening, docking, ADME, MM-GBSA and MD simulation analysis of coumarin derivatives against Methyltransferase (MTase), Endoribonuclease(endoU), ADP ribose Phosphatase and Main Protease enzyme of SARS CoV-2.
All the analysis was performed on Maestro 12.0 Schrodinger software against respective receptors.
Top five compounds of coumarin derivatives s docked at the active site of Methyltransferase (MTase), Endoribonuclease(endoU), ADP ribose Phosphatase and protease and top five compounds of each have docking score from -9.00 to -7.97, -8.42 to -6.80, -8.63 to -7.48 and -7.30 to -6.01 kcal/mol, respectively, of SARS CoV-2.
These compounds were used to analysis of binding free energy by using the Prime MM-GBSA module.
All the compounds showed drug-likeness properties.
MD simulation of Proteins and ligands showed binding stability and good RMSD, radius of gyration of protein, coulomb-SR and LJ-SR energy.
The corrosion inhibition performance of three choline amino acid ionic liquids (ChAAILs) for mild steel in 1 M HCl solution was evaluated by electrochemical analysis, gravimetric measurement, and ...surface morphological characterization in the temperature range of 298–328 K in this paper. The results of the polarization experiments show that ChAAILs affect the cathode and anode reaction processes, proving that ChAAILs are mixed corrosion inhibitors. Choline phenylalanine ionic liquids (ChPhe) exhibit the highest corrosion prevention efficiency among the three chosen corrosion inhibitors, as proven by SEM/EDS scanning, XPS analysis, and molecular dynamics simulation. The values of standard free energy of adsorption ΔGads range between − 20 kJ·mol-1 and − 40 kJ·mol-1, showing that inhibitor molecule adsorption on the metal surface involves both physical and chemical adsorption. According to the results of XPS research and quantum chemical calculations, the adsorption of corrosion inhibitor molecules on the metal surface is strongly related to the anions. The corrosion inhibitor molecules form a thick monolayer adsorption layer on the metal surface, preventing metal-corrosive media interaction. The molecular dynamics simulation findings reveal that the corrosion inhibitor molecules replace the solvent water or any other ions pre-adsorbed on the metal surface during the adsorption process, protecting the metal from corrosion.
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Coronaviruses are contagious pathogens primarily responsible for respiratory and intestinal infections. Research efforts to develop antiviral agents against coronavirus demonstrated the main protease ...(Mpro) protein may represent effective drug target. X-ray crystallographic structure of the SARS-CoV2 Mpro protein demonstrated the significance of Glu166, Cys141, and His41 residues involved in protein dimerization and its catalytic function. We performed in silico screening of compounds from Curcuma longa L. (Zingiberaceae family) against Mpro protein inhibition. Employing a combination of molecular docking, scoring functions, and molecular dynamics simulations, 267 compounds were screened by docking on Mpro crystallographic structure. Docking score and interaction profile analysis exhibited strong binding on the Mpro catalytic domain with compounds C1 (1E,6E)-1,2,6,7-tetrahydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione) and C2 (4Z,6E)-1,5-dihydroxy-1,7-bis(4-hydroxyphenyl)hepta-4,6-dien-3-one as lead agents. Compound C1 and C2 showed minimum binding score (-9.08 and -8.07 kcal/mole) against Mpro protein in comparison to shikonin and lopinavir (≈ −5.4 kcal/mole) a standard Mpro inhibitor. Furthermore, principal component analysis, free energy landscape and protein-ligand energy calculation studies revealed that these two compounds strongly bind to the catalytic core of the Mpro protein with higher efficacy than lopinavir, a standard antiretroviral of the protease inhibitor class. Taken together, this structure based optimization has provided lead on two natural Mpro inhibitors for further testing and development as therapeutics against human coronavirus.
Communicated by Ramaswamy H. Sarma
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•Cyanidin provide a broad range of pharmacological advantages and antioxidant activity as well.•Human serum albumin is responsible for 60% of all plasma proteins essential activities ...as a potential drug carrier.•Holo transferrin is abundant protein within blood plasma which has non-toxicity property.
We examined the inducement of an interaction between two carrier proteins, human serum albumin (HSA) and human holo transferrin (HTF) within the presence of cyanidinin the form of binary and ternary systems, which was conducted by different spectroscopic, isothermal titration calorimetric (ITC), and molecular dynamics simulation techniques. The results of fluorescence spectroscopy verified the occurrence of this interaction by displaying the regular quenching of emission spectra of proteins as single and complex forms by cyanidin. Moreover, fluorescence emission suggested that, HSA-cyanidin, HTF-cyanidin and (HSA-HTF) cyanidin complexes follows an static mechanism with the binding constants of 8.81 × 104, 3.40 × 104, and 7.10 × 104 M−1, respectively, which were strongly reflected to moderate the affinity of cyanidin to both single and complex forms of proteins. The measured thermodynamic parameters obtained by ITC, determined the necessity of electrostatic forces for binding of cyanidin to HSA and HTF. Besides, obtaining a negative ΔG0 is indicative of spontaneous mode of binding process in both conditions. The different values of thermodynamic parameters of cyanidin binding to the forms of HSA, HTF and HSA-HTF complex clearly proved the similarity in the type of interaction forces between cyanidin and proteins as single and complex forms with various values. The observed changes in synchronous fluorescence results were related to the micro-environment properties of Tyr and Trp residues. The induced alternations in the secondary construction of both proteins were confirmed through the outcomes of quantitative analysis performed by circular dichroism spectroscopy (CD) techniques. FRET theory was exerted to calculate, the existing distance across the donor and acceptor, which were reported to be 1.85 nm, 1.97 nm, and 1.91 nm for the cases of HSA-cyanidin, HTF-cyanidin and (HSA-HTF) cyanidin complexes, respectively. Molecular displacement and protein–ligand docking simulations confirmed the binding of cyanidin to HSA and HTF through the binary and ternary systems.
•In silico screening of 177 phytochemicals against RDRP and MPRO against SARS CoV-2.•Insight using molecular docking in terms of interacting residues in binding pocket.•Time dependent stability of ...hits at binding site using molecular dynamic simulations.•Analysis of druggability and oral bioavailability using ADMET and Lipinski filters.
Corona Virus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome coronavirus (SARS CoV-2) has been declared a worldwide pandemic by WHO recently. The complete understanding of the complex genomic structure of SARS CoV-2 has enabled the use of computational tools in search of SARS CoV-2 inhibitors against the multiple proteins responsible for its entry and multiplication in human cells. With this endeavor, 177 natural, anti-viral chemical entities and their derivatives, selected through the critical analysis of the literatures, were studied using pharmacophore screening followed by molecular docking against RNA dependent RNA polymerase and main protease. The identified hits have been subjected to molecular dynamic simulations to study the stability of ligand-protein complexes followed by ADMET analysis and Lipinski filters to confirm their drug likeliness. It has led to an important start point in the drug discovery and development of therapeutic agents against SARS CoV-2.
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