Crystal structure, DFT, molecular docking and dynamics simulation studies of 4,4-dimethoxychalcone

In the current study, the compound 4,4-dimethoxychalcone (DMC) was structurally studied and analyzed by in silico approach against Mpro to investigate its inhibitory potential. The molecular structure of the compound was confirmed by the single crystal X-ray diffraction studies. The crystal structure packing is characterized by various hydrogen bonds, C-H…π and π…π stacking. Intermolecular interactions are quantified by Hirshfeld surface analysis and the electronic structure was optimized by DFT calculations;results are in agreement with the experimental studies. Further, DMC was virtually screened against SARS-CoV-2 main protease (PDB-ID: 6LU7) using molecular docking, and molecular dynamics (MD) simulations to identify its inhibitory potential. A significant binding affinity exists between DMC and Mpro with a-6.00 kcal/mol binding energy. A MD simulation of 30ns was carried out;the results predict DMC possessing strong binding affinity and hydrogen-bonding interactions within the active site during the simulation period. Therefore, based on the results of the current investigation, it can be inferred that a DMC molecule may be able to inhibit Mpro of COVID-19. © 2023 by the authors;licensee Growing Science, Canada.

Exploration of DFT and TD-DFT computation to investigate the interaction between paracetamol and lithium or its compounds.

Paracetamol is a commonly used antipyretic drug and its consumption drastically was increased during the COVID-19 times as fever was one of the symptoms. The excessive usage of paracetamol could harm humans, as the unused accumulated paracetamol can involve in the reaction with many small molecules as well as can interact with several biomolecules. Lithium chloride in its hydrated form is used as an antimanic drug and a geroprotector. It is needed in very small quantities by humans. Tetrahydrated form of lithium ion is the most stable hydrated form. Herein, the authors have investigated the interaction of paracetamol with tetrahydrated lithium chloride (1:1 and 1:2) using the DFT and TD-DFT calculations at 298 K and 310 K. The interaction of paracetamol with lithium chloride P1 (1:1), P2 (2:1), P3 (3:1) and P4 (4:1) are also studied by DFT calculations in default and CPCM model. The authors have calculated the free energy, optimization energy, dipole moment and other thermodynamic parameters of all the systems. Based on enthalpy and change in Gibbs free energy, the interaction was maximum between the paracetamol and tetrahydrated lithium chloride at 298 K as well as 310 K which indicates that the hydrated lithium chloride is being consumed by unused paracetamol. In P1 and P3, lithium showed interaction with oxygen of phenolic group and other atoms of all the paracetamol molecules present, while in P2 and P4, lithium showed these interactions with only one paracetamol molecule.

Naphtho[2,1-b]furan derived triazole-pyrimidines as highly potential InhA and Cytochrome c peroxidase inhibitors: Synthesis, DFT calculations, drug-likeness profile, molecular docking and dynamic studies

Napthofuran and its fused heterocyclic derivatives evaluated with varied biological activity functional groups comprise an important class of compounds for new chemical entities. We here in reporting synthesis of new 3-(4-substituted phenyl)naphtho[1′,2′:4,5]furo[2,3-e][1,2,4]triazolo[4,3-c]pyrimidines 6(a-f). Structures of the newly synthesized compounds were confirmed by making use of spectroscopic techniques like IR, NMR and Mass. The DFT calculations were taken for the selected molecules using B3LYP hybrid functional with a 6–31+G (d, p) all-electron basis set using the Gaussian 09 package. The bioactivity predictions were evaluated for the synthesized compounds. The In vitro biological activities were reported for the all compounds 6(a-f). The compound 6a showed high activity of anti-TB and antioxidant activity with at MIC 1.6 μg/ml and at percentage of inhibition (72.54±0.21) at 10μg/ml respectively. The compound 6f (73.21±0.11) showed antioxidant activity better than standard drug BHA (71.32±0.13) at 10 μg/ml. Furthermore, the docking studies for the newly synthesized molecules were carried out by Auto dock software with proteins InhA (4TZK),Cytochrome c peroxidase (2 × 08) and protease (Mpro) of SARS-CoV-2 Omicron (PDB ID: 7TOB). All the compounds showed a strong binding affinity for the docked proteins. The outcome of docking results showed that compound 6ahad excellent binding energies -10.8, -9.4, and -9.0 kcal/mol with 4TZK, 2 × 08, and 7TOB respectively. Lastly, the protein stability, fluctuations of APO-Protein, protein-ligand complexes were investigated through Molecular Dynamics (MD) simulations studies using Desmond Maestro 11.3 and potential lead molecules were identified. © 2023

Structural and Computational Studies of Cobalt(II) and Copper(II) Complexes with Aromatic Heterocyclic Ligand

Two coordination complexes, a cobalt(II) complex tris(1,10-phenanthroline)-cobalt perchlorate hydrate, [Co(phen)3]·(ClO4)2·H2O(1), and a copper(II) complex tris(1,10-phenanthroline)-copper perchlorate 4-bromo-2-{[(naphthalene-1-yl)imino]methyl}phenol hydrate, [Cu(phen)3]·(ClO4)2·HL·[O] (2), [where, phen = 1,10-phenathroline as aromatic heterocyclic ligand, HL = 4-bromo-2-((Z)-(naphthalene-4-ylimino) methyl) phenol] have been synthesized and structurally characterized. Single crystal X-ray analysis of both complexes has revealed the presence of a distorted octahedral geometry around cobalt(II) and copper(II) ions. density functional theory (DFT)-based quantum chemical calculations were performed on the cationic complex [Co(phen)3]2+ and copper(II) complex [Cu(phen)3]2+ to get the structure property relationship. Hirshfeld surface and 2-D fingerprint plots have been explored in the crystal structure of both the metal complexes. To find potential SARS-CoV-2 drug candidates, both the complexes were subjected to molecular docking calculations with SARS-CoV-2 virus (PDB ID: 7BQY and 7C2Q). We have found stable docked structures where docked metal chelates could readily bound to the SARS-CoV-2 Mpro. The molecular docking calculations of the complex (1) into the 7C2Q-main protease of SARS-CoV-2 virus revealed the binding energy of −9.4 kcal/mol with a good inhibition constant of 1.834 µM, while complex (2) exhibited the binding energy of −9.0 kcal/mol, and the inhibition constant of 1.365 µM at the inhibition binding site of receptor protein. Overall, our in silico studies explored the potential role of cobalt(II) complex (1), and copper(II) complex (2) complex as the viable and alternative therapeutic solution for SARS-CoV-2.

A dispersion-corrected DFT calculation on encapsulation of favipiravir drug used as antiviral against COVID-19 into carbon-, boron-, and aluminum-nitride nanotubes for optimal drug delivery systems combined with molecular docking simulations.

Favipiravir (FAV) (6-fluoro-3-oxo-3,4-dihydropyrazine-2-carboxamide) is one of the most effective antiviral drugs which is cited for action against RNA-viral infections of COVID-19. In this study, density functional theory (DFT) calculations were used to investigate three nanotubes (NTs) with FAV drug as delivery systems. The encapsulated systems (ESs) consist of FAV drug inside carbon-carbon, aluminum nitride, and boron nitride. At B3LYP-D/6-31G(d,p) and CPCM/B3LYP-D/6-31G(d,p), the optimization of NTs, FAV, and its tautomeric forms and six ESs was investigated in gas and water environments. Five tautomeric forms of FAV were investigated, two keto forms (K1 and K2) and three enol forms (E1, E2, and E3). The results revealed that E3 and K2 isomeric forms represented the most stable structures in both media; thus, these two forms were encapsulated into the NTs. The stability and the synthesis feasibility of NTs have been proven by calculating their interaction energies. Non-covalent interactions (NCIs) were investigated in the ESs to show the type of NCI with the molecular voids. The binding energies, thermochemical parameters, and recovery times were investigated to understand the mechanism of FAV encapsulation and release. The encapsulated AlNNT systems are more favorable than those of BNNTs and CNTs in gas and aqueous environments with much higher binding energies. The quantum theory of atoms in molecules (QTAIM) and recovery time analysis revealed the easier releasing of E3 from AlNNT over K2 form. Based on molecular docking simulations, we found that E3 and K2 FAV forms showed a high level of resistance to SARS-CoV-6M3M/6LU7/6W9C proteases. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-023-02182-4.

Investigate the designing of eutectic mixture using DFT computation and evaluate their biological potency using molecular docking

Researchers are exploring the eutectic mixture because of their obvious great potential in various disciplines. Herein, authors have presented the DFT calculations, molecular docking and QSAR results for designed eutectic mixtures (EMs) using thiourea and resorcinol on taking different equivalent ratio. Authors have used Jakob et al. method to determine the melting temperature of the systems or EMs theoretically. Thermodynamic parameteres such as the free energy, enthalpy, and other energy of the EMs at room temperature are determined through DFT calculations using Gaussian. Authors have also calculated the physiochemical descriptors of various eutectic mixture based on DFT calculations. Further, molecular docking of the designed EMs is carried out to investigate their biological potential for inhibition of the Mpro of SARS-CoV-2. © 2023 Elsevier B.V.

Novel pyrimidines as COX-2 selective inhibitors: synthesis, DFT analysis, molecular docking and dynamic simulation studies.

Pyrimidine and its derivatives are associated with varieties of biological properties. Therefore, we herein reported the synthesis of four novel pyrimidines (2, 3, and 4a, b) derivatives. The structure of these molecules is confirmed by spectroscopic methods such as IR, NMR, and Mass analysis. The electronic behavior of synthesized compounds 4a, b and in silico drug design 4 c, d was explained by Density Functional Theory estimations at the DFT/B3LYP level via 6-31 G++ (d, p) replicates the structure and geometry. All the synthesized compounds were screened for their in vitro COX-1 and COX-2 inhibitory activity compared to standards Celecoxib and Ibuprofen. Compounds 3 and 4a afforded excellent COX-1 and COX-2 inhibitory activities at IC50 = 5.50 and 5.05 µM against COX-1, 0.85 and 0.65 µM against COX-2, respectively. The standard drugs Celecoxib and Ibuprofen showed inhibitory activity at IC50 = 6.34 and 3.1 µM against COX-1, 0.56 and 1.2 µM against COX-2, respectively. Further, these compounds showed high potential docking with SARS-CoV-2 Omicron protease & COX-2 and predicted drug-likeness for the pyrimidine analogs by using Molinspiration. The protein stability, fluctuations of APO-protein, protein-ligand complexes were investigated through Molecular Dynamics simulations studies using Desmond Maestro 11.3 and potential lead molecules were identified.Communicated by Ramaswamy H. Sarma.

Design, synthesis, and computational studies of novel imidazo[1,2-a]pyrimidine derivatives as potential dual inhibitors of hACE2 and spike protein for blocking SARS-CoV-2 cell entry.

In the present work, a new series of imidazo[1,2-a]pyrimidine Schiff base derivatives have been obtained using an easy and conventional synthetic route. The synthesized compounds were spectroscopically characterized using 1H, 13C NMR, LC-MS(ESI), and FT-IR techniques. Green metric calculations indicate adherence to several green chemistry principles. The energy of Frontier Molecular Orbitals (FMO), Molecular Electrostatic Potential (MEP), Quantum Theory of Atoms in Molecules (QTAIM), and Reduced Density Gradient (RDG) were determined by the Density Functional Theory (DFT) method at B3LYP/6-31 G (d, p) as the basis set. Moreover, molecular docking studies targeting the human ACE2 and the spike, key entrance proteins of the severe acute respiratory syndrome coronavirus-2 were carried out along with hACE2 natural ligand Angiotensin II, the MLN-4760 inhibitor as well as the Cannabidiolic Acid CBDA which has been demonstrated to bind to the spike protein and block cell entry. The molecular modeling results showed auspicious results in terms of binding affinity as the top-scoring compound exhibited a remarkable affinity (-9.1 and -7.3 kcal/mol) to the ACE2 and spike protein respectively compared to CBDA (-5.7 kcal/mol), the MLN-4760 inhibitor (-7.3 kcal/mol), and angiotensin II (-9.2 kcal/mol). These findings suggest that the synthesized compounds may potentially act as effective entrance inhibitors, preventing the SARS-CoV-2 infection of human cells. Furthermore, in silico, ADMET, and drug-likeness prediction expressed promising drug-like characteristics.

A comparative DFT study on Al- and Si- doped single-wall carbon nanotubes (SWCNTs) for Ribavirin drug sensing and detection

In this work, we have presented a comparative study on Ribavirin (RBV) drug sensing and detection on the pristine and functionalized single-wall carbon nanotubes (f-SWCNTs) by Density Functional Theory (DFT) method. The pristine and metal-doped zigzag (4,0) and (6,0) SWCNTs were first considered for the RBV adsorption. All the probable positions of RBV adsorption were investigated to find which one is energetically favourable. The topology analysis of the Quantum theory of atoms in a molecule (QTAIM) with non-covalent interactions (NCI-RDG), Frontier molecular orbitals (FMO), Density of states (DOS), and non-linear optical (NLO) analysis were carried out to understand the molecular structure, electrical, electronic and optical properties of complexes. The charge analysis indicates that charge transfer is from the adsorbed RBV to the pristine and metal-doped (4,0) and (6,0) SWCNTs. The highest values of adsorption energies for Al-, Si-doped and pristine (4,0) SWCNTs were determined as −34.688, −87.999 and −10.382 kcal/mol, respectively, whereas corresponding values for metal-doped and pristine (6,0) SWCNTs are about −43.592, −20.661 and −12.414 kcal/mol, respectively. The results suggest that those bare and metal-doped (4,0) SWCNTs and (6,0) Si-SWCNTs can serve as promising sensors in practical applications to detect, recognize and carrier RBV drug for its medicinal drug delivery applications. Based on the NLO properties of (6,0) Si-SWCNTs and pristine (6,0) SWCNT (with an acceptable recovery time of 279s and first hyper polarizability value of β = 229.25 × 10−30 cm5 esu−1), those nanotubes may be possible candidates to be used as the optoelectronic sensor for RBV drug. The appropriate short length of nanotubes was obtained. © Elsevier Ltd

In a search for potential drug candidates for combating COVID-19: computational study revealed salvianolic acid B as a potential therapeutic targeting 3CLpro and spike proteins.

The global prevalence of COVID-19 disease and the overwhelming increase in death toll urge scientists to discover new effective drugs. Although the drug discovery process is a challenging and time-consuming, fortunately, the plant kingdom was found to have many active therapeutics possessing broad-spectrum antiviral activity including those candidates active against severe acute respiratory syndrome coronaviruses (SARS-CoV). Herein, nine traditional Chinese medicinal plant constituents from different origins (Glycyrrhizin 1, Lycorine 2, Puerarin 3, Daidzein 4, Daidzin 5, Salvianolic acid B 6, Dihydrotanshinone I 7, Tanshinone I 8, Tanshinone IIa 9) previously reported to exhibit antiviral activity against SARS-CoV were virtually screened in silico (molecular docking) as potential inhibitors of SARS-CoV-2 target proteins. The tested medicinal plant compounds were in silico screened for their activity against two key SARS-CoV-2 target proteins; 3CLpro, and Spike binding-domain proteins. Among the tested medicinal plant compounds, Salvianolic acid B 6 (Sal-B) showed promising binding affinities against the two specified SARS-CoV-2 target proteins compared to the reference standards used. Hence molecular dynamics simulations followed by calculating the free-binding energy were carried out for Sal-B providing information on its affinity, stability, and thermodynamic behavior within the two SARS-CoV-2 target proteins as well as key ligand-protein binding aspects. Besides, the quantum mechanical calculations showed that Sal-B can adopt different conformations due to the existence of various rotatable bonds. Therefore, the enhanced antiviral activity of Sal-B among other studied compounds can be also attributed to the structural flexibility of Sal-B. Our study gives an explanation of the structure activity relationship required for targeting SARS-CoV-2 3CLpro and Spike proteins and also facilitates the future design and synthesis of new potential drugs exhibiting better affinity and specificity. Besides, an ADME study was carried out on screened compounds and reference controls revealing their pharmacokinetics properties.Communicated by Ramaswamy H. Sarma.

DFT and In-silico Investigations along with In-vitro Antitumor and Antimicrobial Assessments of Pharmacological Molecules.

BACKGROUND: Molecules, bearing an active methylene bridge, are deemed to be one of the most fruitful and remarkable precursors that have been incorporated in the synthetic strategy of an assortment of bioactive compounds. OBJECTIVE: The reactive methylene derivatives have been endowed with multiple reactions, which target biological and medicinal applications and are resultant from their structural multiplicity and discrete reactivity. METHODS: The present report endeavors to synthesize, characterize, and in-vitro evaluate several novel propanoic acid, coumarin, and pyrazole derivatives as antimicrobial and antiproliferative agents. The in-silico molecular docking, physicochemical, pharmacokinetic/ADMET, bioactivity, and drug likeness predictions were conducted for all the synthesized compounds. RESULTS: The highest docking score is -9.9 and -8.3 kcal/mol respectively for compound 9 (azo-coumarin) and 13 (acrylic acid derivative) with the target proteins E. coli topoisomerase II, DNA gyrase subunit B and PI3K p110α domain, respectively. Moreover, this study predicts the synthesized molecules that may inhibit the novel COVID-19, obtained through virtual screenings only, where compounds 9, 13, 14, 17, and 19 came to the limelight with good docking scores i.e more than 8 Kcal/mol. Safety profiling of the most potent compound 9 was utilized against normal cell line and hemolytic effect on RBCs. CONCLUSION: The in-silico ADMET studies of the synthesized compounds revealed moderate to good drug likeness, high gastro intestinal (GI) absorption, inhibits the Cytochrome CYP2C19 and CYP2C9 and all the derivatives possess non-cancerous nature. The in-vitro screening demonstrated that several of the novel molecules are promising drug candidates. The density function theory (DFT) theoretical calculations were performed to calculate the energy levels of the FMOs and their energy gabs, dipole moment as well as the molecular electrostatic potential. Such parameters along with the physicochemical parameters could be good tool to confirm the biological activity.

Synthesis, X-ray crystal structure, Hirshfeld surface analysis and computational investigation into the potential inhibitory action of novel 6-(p-tolyl)-2-((p-tolyl)thio)methyl-7H-[1.2.4]triazolo[5,1-b][1,3,4]thiadiazine inhibits the main protease of COVID-19.

In recent times, the novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become a worldwide pandemic. With over 71 million confirmed cases, even though the effectiveness and side effects of the specific drugs and vaccines approved for this disease are still limited. Scientists and researchers from all across the world are working to find a vaccine and a cure for COVID-19 by using large-scale drug discovery and analysis. Heterocyclic compounds are regarded to be valuable sources for the discovery of new antiviral medications against SARS-CoV-2 because virus occurrences are still on the rise, and infectivity and mortality may also rise shortly. In this regard, we have synthesized a new triazolothiadiazine derivative. The structure was characterized by NMR spectra and confirmed by X-ray diffraction analysis. The structural geometry coordinates of the title compound are well reproduced by DFT calculations. NBO and NPA analyses have been performed to determine the interaction energies between bonding and antibonding orbital, and natural atomic charges of heavy atoms. Molecular docking suggests that the compounds may have good affinity for SAR-CoV-2 main protease, RNA-dependent RNA polymerase and nucleocapsid enzymes, particularly the main protease enzyme (binding energy of -11.9 kcal mol-1). The predicted docked pose of the compound is dynamically stable and reports a major van der Waals contribution (-62.00 kcal mol-1) to overall net energy.Communicated by Ramaswamy H. Sarma.

Adsorption of Molnupiravir anti-COVID-19 drug over B12N12 and Al12N12 nanocarriers: a DFT study.

The potentiality of B12N12 and Al12N12 nanocarriers to adsorb Molnupiravir anti-COVID-19 drug, for the first time, was herein elucidated using a series of quantum mechanical calculations. Density function theory (DFT) was systematically utilized. Interaction (Eint) and adsorption (Eads) energies showed higher negative values for Molnupiravir···Al12N12 complexes compared with Molnupiravir···B12N12 analogs. Symmetry-adapted perturbation theory (SAPT) results proclaimed that the adsorption process was predominated by electrostatic forces. Notably, the alterations in the distributions of the molecular orbitals ensured that the B12N12 and Al12N12 nanocarriers were efficient candidates for delivering the Molnupiravir drug. From the thermodynamic perspective, the adsorption process of Molnupiravir drug over B12N12 and Al12N12 nanocarriers had spontaneous and exothermic nature. The ESP, QTAIM, NCI, and DOS observations exposed the tendency of BN and Al12N12 to adsorb the Molnupiravir drug. Overall, these findings proposed that the B12N12 and Al12N12 nanocarriers are efficient aspirants for the development of the Molnupiravir anti-COVID-19 drug delivery process.Communicated by Ramaswamy H. Sarma.

A comparative DFT study on Al- and Si- doped single-wall carbon nanotubes (SWCNTs) for Ribavirin drug sensing and detection

In this work, we have presented a comparative study on Ribavirin (RBV) drug sensing and detection on the pristine and functionalized single-wall carbon nanotubes (f-SWCNTs) by Density Functional Theory (DFT) method. The pristine and metal-doped zigzag (4,0) and (6,0) SWCNTs were first considered for the RBV adsorption. All the probable positions of RBV adsorption were investigated to find which one is energetically favourable. The topology analysis of the Quantum theory of atoms in a molecule (QTAIM) with non-covalent interactions (NCI-RDG), Frontier molecular orbitals (FMO), Density of states (DOS), and non-linear optical (NLO) analysis were carried out to understand the molecular structure, electrical, electronic and optical properties of complexes. The charge analysis indicates that charge transfer is from the adsorbed RBV to the pristine and metal-doped (4,0) and (6,0) SWCNTs. The highest values of adsorption energies for Al-, Si-doped and pristine (4,0) SWCNTs were determined as −34.688, −87.999 and −10.382 kcal/mol, respectively, whereas corresponding values for metal-doped and pristine (6,0) SWCNTs are about −43.592, −20.661 and −12.414 kcal/mol, respectively. The results suggest that those bare and metal-doped (4,0) SWCNTs and (6,0) Si-SWCNTs can serve as promising sensors in practical applications to detect, recognize and carrier RBV drug for its medicinal drug delivery applications. Based on the NLO properties of (6,0) Si-SWCNTs and pristine (6,0) SWCNT (with an acceptable recovery time of 279s and first hyper polarizability value of β = 229.25 × 10−30 cm5 esu−1), those nanotubes may be possible candidates to be used as the optoelectronic sensor for RBV drug. The appropriate short length of nanotubes was obtained.

Unraveling the Intrinsic Biocidal Activity of the SiO2-Ag Composite against SARS-CoV-2: A Joint Experimental and Theoretical Study.

The COVID-19 pandemic has emerged as an unprecedented global healthcare emergency, demanding the urgent development of effective materials to inactivate the SARS-CoV-2 virus. This research was planned to disclose the remarkable biocidal activity of SiO2-Ag composites incorporated into low-density polyethylene. For this purpose, a joint experimental and theoretical [based on first-principles calculations at the density functional theory (DFT) level] study is performed. Biological assays showed that this material eliminatesStaphylococcus aureusand SARS-CoV-2 virus in just 2 min. Here, we investigate a previously unexplored process that we postulate may occur along the O2 and H2O adsorption and activation processes of pure and defective SiO2-Ag surfaces for the generation of reactive oxygen species (ROS). The obtained results help us to predict the nature of ROS: superoxide anion radicals, •O2-, hydroxyl radicals, •OH, and hydroperoxyl radicals, •HO2, that destroy and degrade the structure of the SARS-COV-2 virus. This is consistent with the DFT studies, where the energetic, electronic, and magnetic properties of the intermediates show a feasible formation of ROS. Present findings are expected to provide new insights into the relationship among the structure, property, and biocidal activity of semiconductor/metal SiO2-Ag composites.

Study the effect of antioxidants on biological activity and on homopolypropylene, mechanical and physical properties

Exposure of polymers to temperature, atmospheric oxygen, or even light could result in some degradation of the polymer properties and features during processing (application), storage and end use. In hydrocarbon polymers, the polymer tend to free radical formation, eventually resulting in chain damage or crosslinking that leads to degradation. Antioxidants are used to terminate these chain reactions by removing radicals. Antioxidants are used in most hydrocarbon polymers including, polypropylene. a good addiction package must be existed to overcome the effect of degradation and save the polymer shape and characteristics. The practical experiment was carried out on a pure polypropylene (intermediate polypropylene resin without additives) and another practical experiment but with adding several types of additives with a certain concentration and study the behavior of polypropylene in all cases with successive extrusions. On other hand Flexible molecular docking on heme oxy-genase, an important stress protein that is involved in cellular protection, antioxidant and anti-inflammatory activities, justified the antioxidant activity of the isolated compounds. From the binding energy 3114 and 1680 they could consider to be powerful and available antioxidant.

Investigation of embelin synthetic hybrids as potential COVID-19 and COX inhibitors: Synthesis, spectral analysis, DFT calculations and molecular docking studies.

Embelin (2, 5-dihydroxy-3-undecyl-1,4-benzoquinone), a benzoquinone isolated from fruits of Embelia ribes has miscellaneous biological potentials including; anticancer, anti-inflammation, antibiotic, and anti-hyperglycemic activities. Also, embelin down-regulates the overexpression of inflammatory pathways like NF-kB, TACE, TNF-α, and other cytokines. Furthermore, embelin fascinated synthetic interest as a pharmacologically active compound. The present article involves the design, synthesis, DFT calculations, and molecular docking studies of embelin derivatives as cyclooxygenase inhibitors of embelin derivatives. The structure of these derivatives is confirmed by the various spectral analyses such as IR, NMR, and Mass. The DFT calculations were carried out for the molecules (1-8) using CAM-B3LYP hybrid functional with a 6-31+g(d) all-electron basis set using the Gaussian 09 package. Second-order harmonic vibrational calculations are used to check the minimum nature of the geometry. Further, HOMO and LUMO analyses were used for the charge transfer interface between the structures. Based on our previous work and structural activity relationship study, foresaid embelin derivatives were evaluated for in vitro COX-1 and COX-2 inhibitory activity. The compounds 3, 4, 7, and 8 demonstrated excellent COX inhibitions with IC50 values of 1.65, 1.54, 1.56, and 1.23 µM compared to standard drugs Celecoxib and Ibuprofen. Finally, the molecular docking studies carried out with Covid-19 and cyclooxygenase with all the newly synthesized embelin derivatives.

Reactivity and binding mode of disulfiram, its metabolites, and derivatives in SARS-CoV-2 PLpro: insights from computational chemistry studies.

The papain-like protease (PLpro) from SARS-CoV-2 is an important target for the development of antivirals against COVID-19. The safe drug disulfiram (DSF) presents antiviral activity inhibiting PLpro in vitro, and it is under clinical trial studies, indicating to be a promising anti-COVID-19 drug. In this work, we aimed to understand the mechanism of PLpro inhibition by DSF and verify if DSF metabolites and derivatives could be potential inhibitors too. Molecular docking, DFT, and ADMET techniques were applied. The carbamoylation of the active site cysteine residue by DSF metabolite (DETC-MeSO) is kinetically and thermodynamically favorable (ΔG‡ = 3.15 and ΔG = - 12.10 kcal mol-1, respectively). Our results strongly suggest that the sulfoxide metabolites from DSF are promising covalent inhibitors of PLpro and should be tested in in vitro and in vivo assays to confirm their antiviral action.

In silico studies of Mpro and PLpro from SARS-CoV-2 and a new class of cephalosporin drugs containing 1,2,4-thiadiazole.

The SARS-CoV-2 proteases Mpro and PLpro are important targets for the development of antivirals against COVID-19. The functional group 1,2,4-thiadiazole has been indicated to inhibit cysteinyl proteases, such as papain and cathepsins. Of note, the 1,2,4-thiadiazole moiety is found in a new class of cephalosporin FDA-approved antibiotics: ceftaroline fosamil, ceftobiprole, and ceftobiprole medocaril. Here we investigated the interaction of these new antibiotics and their main metabolites with the SARS-CoV-2 proteases by molecular docking, molecular dynamics (MD), and density functional theory (DFT) calculations. Our results indicated the PLpro enzyme as a better in silico target for the new antibacterial cephalosporins. The results with ceftaroline fosamil and the dephosphorylate metabolite compounds should be tested as potential inhibitor of PLpro, Mpro, and SARS-CoV-2 replication in vitro. In addition, the data here reported can help in the design of new potential drugs against COVID-19 by exploiting the S atom reactivity in the 1,2,4-thiadiazole moiety. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-02036-5.

Synthesis, characterization, theoretical study and molecular docking studies of some new cobalt(II), chromium(II) and nickel (II) complexes

Three transition metal complexes with general formula [M(L)(2)] (Co = (1), Cr = (2) and Ni = (3)), were synthesized by treating CoCl2/CrCl3 center dot 6H(2)O/NiCl2 center dot 6H(2)O with an ONS-donor Schiff base ligand (HL) derived from the condensation of 3,5-Diiodosalicylaldehyde and 4,4-Dimethyl-3-thiosemicarbazide. The geometry around the centre metal ions was octahedral as revealed by the data collection from spectroscopic studies. The newly synthesized compounds were fully characterized by various physicochemical and spectroscopic methods. DFT calculations were performed on the compounds to get a structure-property relationship. Some global reactivity descriptors like chemical potential (mu), electronegativity (chi), hardness (eta) and electrophilicity index (omega) were also evaluated using DFT method. The ADMET prediction analyses have been explored. Molecular dynamics simulations were also studied. Besides this, to find a potential inhibitor for anti-SARS-CoV-2, metal complexes are also assessed through molecular docking and 3-D visualizations of intermolecular interactions against main protease (M-pro) of SARS-CoV-2 (PDB ID: 7JKV). The molecular docking calculations of the complex (1) into the main protease of SARS-CoV-2 virus (PDB ID: 7JKV) revealed the binding energy of -7.2 kcal/mol with an inhibition constant of 2.529 mu M at inhibition binding site of receptor protein. Complex (2) with SARS-CoV-2 resulted in the binding energy of -7.8 kcal/mol and the inhibition constant of 5.231 mu M. Similarly, complex (3) with SARS-CoV-2 (PDB ID: 7JKV) exhibited the binding energy and the inhibition constant of -7.5 kcal/mol and 3.585 mu M respectively at inhibition binding site of receptor protein. Overall, in silico studies explored the potential role of metal complexes, which would offer new drug candidates against SARS-CoV-2.