Minimum Binding Energy Research Articles

Synthesis, Biological Evaluation and Molecular Modeling of Pyrazole-Phthalazine Hybrid Derivatives Bearing 2-Aryloxy Quinoline Nucleus and their Computational Quantum Mechanical Modelling

In present work, the synthesis, characterization, antibacterial and anticancer activities of a novel series of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives bearing 2-aryloxyquinoline nucleus (6a-l) is reported. In vitro antibacterial and anticancer activities against used strains and two cell lines A549 and HepG2 as well as enzyme inhibitory activities against EGFR and FabH were carried out. The most potent inhibitory activity against EGFR was displayed by compound 6l and against FabH by compound 6i. Docking studies showed that compound 6l was bound to the active pocket of EGFR with hydrogen bond and π-H interaction with minimum binding energy and compound 6i was bound to the active site of FabH with hydrogen bond and π-H interaction having minimum binding energy. DFT studies explained spatial arrangement as well as HOMO-LUMO to evaluate the plane angle. On the basis of their substitutions, these plane angles were then related with their activity against EGFR and FabH as well as antibacterial and anticancer activities.

Construction of a three commitment points for S phase entry cell cycle model and immune-related ceRNA network to explore novel therapeutic options for psoriasis.

While competing endogenous RNAs (ceRNAs) play pivotal roles in various diseases, the proliferation and differentiation of keratinocytes are becoming a research focus in psoriasis. Therefore, the three commitment points for S phase entry (CP1-3) cell cycle model has pointed to a new research direction in these areas. However, it is unclear what role ceRNA regulatory mechanisms play in the interaction between keratinocytes and the immune system in psoriasis. In addition, the ceRNA network-based screening of potential therapeutic agents for psoriasis has not been explored. Therefore, we used multiple bioinformatics approaches to construct a ceRNA network for psoriasis, identified CTGF as the hub gene, and constructed a ceRNA subnetwork, after which validation datasets authenticated the results' accuracy. Subsequently, we used multiple online databases and the single-sample gene-set enrichment analysis algorithm, including the CP1-3 cell cycle model, to explore the mechanisms accounting for the increased proliferation and differentiation of keratinocytes and the possible roles of the ceRNA subnetwork in psoriasis. Next, we performed cell cycle and cell trajectory analyses based on a single-cell RNA-seq dataset of psoriatic skin biopsies. We also used weighted gene co-expression network analysis and single-gene batch correlation analysis-based gene set enrichment analysis to explore the functions of CTGF. Finally, we used the Connectivity Map to identify MS-275 (entinostat) as a novel treatment for psoriasis, SwissTargetPrediction to predict drug targets, and molecular docking to investigate the minimum binding energy and binding sites of the drug to target proteins.

Synthesis and Evaluation of the Antibacterial and Antioxidant Activities of Some Novel Chloroquinoline Analogs

Quinoline heterocycle is a useful scaffold to develop bioactive molecules used as anticancer, antimalaria, and antimicrobials. Inspired by their numerous biological activities, an attempt was made to synthesize a series of novel 7-chloroquinoline derivatives, including 2,7-dichloroquinoline-3-carbonitrile (5), 2,7-dichloroquinoline-3-carboxamide (6), 7-chloro-2-methoxyquinoline-3-carbaldehyde (7), 7-chloro-2-ethoxyquinoline-3-carbaldehyde (8), and 2-chloroquinoline-3-carbonitrile (12) by the application of Vilsmeier–Haack reaction and aromatic nucleophilic substitution of 2,7-dichloroquinoline-3-carbaldehyde. The carbaldehyde functional group was transformed into nitriles using POCl3 and NaN3, which was subsequently converted to amide using CH3CO2H and H2SO4. The compounds synthesized were screened for their antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes. Compounds 6 and 8 showed good activity against E. coli with an inhibition zone of 11.00 ± 0.04 and 12.00 ± 0.00 mm, respectively. Compound 5 had good activity against S. aureus and P. aeruginosa with an inhibition zone of 11.00 ± 0.03 mm relative to standard amoxicillin (18 ± 0.00 mm). Compound 7 displayed good activity against S. pyogenes with an inhibition zone of 11.00 ± 0.02 mm. The radical scavenging activity of these compounds was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), and compounds 5 and 6 displayed the strongest antioxidant activity with IC50 of 2.17 and 0.31 µg/mL relative to ascorbic acid (2.41 µg/mL), respectively. The molecular docking study of the synthesized compounds was conducted to investigate their binding pattern with topoisomerase IIβ and E. coli DNA gyrase B. Compounds 6 (−6.4 kcal/mol) and 8 (−6.6 kcal/mol) exhibited better binding affinity in their in silico molecular docking against E. coli DNA gyrase. The synthesized compounds were also found to have minimum binding energy ranging from −6.9 to −7.3 kcal/mol against topoisomerase IIβ. The SwissADME predicted results showed that the synthesized compounds 5–8 and 12 satisfy Lipinski’s rule of five with zero violations. The ProTox-II predicted organ toxicity results revealed that all the synthesized compounds were inactive in hepatotoxicity, immunotoxicity, mutagenicity, and cytotoxicity. The findings of the in vitro antibacterial and molecular docking analysis suggested that compound 8 might be considered a hit compound for further analysis as antibacterial and anticancer drug. The radical scavenging activity displayed by compounds 5 and 6 suggests these compounds as a radical scavenger.

First-principles study of metal-semiconductor contact OF CS and X2CO2 (X=Ti, Zr, Hf) monolayers

Using first principles calculations, we have investigated the structural and electronic properties of Carbon Sulfide (CS) and X2CO2 (X=Ti, Zr, Hf) MXenes monolayers and their CS-X2CO2 (X=Ti, Zr, Hf) metal-semiconductor (MS) contacts. The energetic stability of MS contacts is confirmed by minimum binding energy. The intrinsic electronic properties of CS-X2CO2 are well preserved due to weak van der Waals (vdWs) contact. An indirect band gap semiconductor behavior is found for Ti2CO2, Zr2CO2, Hf2CO2, while CS and all MS contacts are metals. Our results show that the interface CS-X2CO2formed p-type Schottky contact with a SBH of 0.69 eV. Furthermore, we also compute the electrostatic potential for CS-X2CO2 MS contacts, where the CS layer have deeper potential than X2CO2 layer and the electrons/charges of CS-X2CO2 MS contacts transfer from CS layer to X2CO2 monolayer. Also, we calculate the work function of CS-X2CO2 (X=Ti, Zr, Hf) MS contacts, which corresponds to minimum amount of energy required to remove an electron from the metal. These results will be useful for promising applications in field-effect transistors (FET) and photodetectors devices.

Synthesis, DFT Analysis, and Evaluation of Antibacterial and Antioxidant Activities of Sulfathiazole Derivatives Combined with In Silico Molecular Docking and ADMET Predictions.

Synthetic modifications of sulfathiazole derivatives become an interesting approach to enhance their biological properties in line with their applications. As a result, sulfathiazole derivatives become a good candidate and potential class of organic compounds to play an important role towards medicinal chemistry. In present study, one thiazole derivative and two new sulfathiazole derivatives are synthesized with 94% and 72–81% yields, respectively. Furthermore, the synthesized compounds were evaluated for their in vitro antibacterial activity against two Gram-negative (E. coli and P. aeruginosa) and two Gram-positive bacterial strains (S. pyogenes and S. aureus) by disk diffusion method. Among synthesized compounds, compound 11a showed potent inhibitory activity against Gram-negative, E. coli with 11.6 ± 0.283 mm zone of inhibition compared to standard drug sulfamethoxazole (15.7 ± 0.707 mm) at 50 mg/mL. The radical scavenging activities of these compounds were evaluated using DPPH radical assay, and compound 11a showed the strongest activity with IC50 values of 1.655 μg/mL. The synthesized compounds were evaluated for their in silico molecular docking analysis using S. aureus gyrase (PDB ID: 2XCT) and human myeloperoxidase (PDB ID: 1DNU) and were found to have minimum binding energy ranging from −7.8 to −10.0 kcal/mol with 2XCT and −7.5 to −9.7 with 1DNU. Compound 11a showed very good binding score −9.7 kcal/mol with both of the proteins and had promising alignment with in vitro results. Compound 11b also showed high binding scores with both proteins. Drug likeness and ADMET of synthesized compounds were predicted. The DFT analysis of synthesized compounds was performed using Gaussian 09 and visualized through Gauss view 6.0. The structural coordinates of the lead compounds were optimized using B3LYP/6–31 G (d,p) level basis set without any symmetrical constraints. Studies revealed that all the synthesized compounds might be candidates for further antibacterial and antioxidant studies.

Exploring the therapeutic nature of limonoids and triterpenoids against SARS-CoV-2 by targeting nsp13, nsp14, and nsp15 through molecular docking and dynamics simulations

Background and aimThe ongoing global pandemic due to SARS-CoV-2 caused a medical emergency. Since December 2019, the COVID-19 disease is spread across the globe through physical contact and respiratory droplets. Coronavirus caused a severe effect on the human immune system where some of the non-structural proteins (nsp) are involved in virus-mediated immune response and pathogenesis. To suppress the viral RNA replication mechanism and immune-mediated responses, we aimed to identify limonoids and triterpenoids as antagonists by targeting helicases (nsp13), exonuclease (nsp14), and endoribonuclease (nsp15) of SARS-CoV-2 as therapeutic proteins. Experimental procedureIn silico molecular docking and drug-likeness of a library of 369 phytochemicals from limonoids and triterpenoids were performed to screen the potential hits that binds effectively at the active site of the proteins target. In addition, the molecular dynamics simulations of the proteins and their complexes with the potential hits were performed for 100 ns by using GROMACS. Results and conclusionThe potential compounds 26-deoxyactein and 25-O-anhydrocimigenol 3-O-beta-d-xylopyranoside posing strong interactions with a minimum binding energy of −10.1 and −9.5 kcal/mol, respectively and sustained close contact with nsp13 for 100 ns. The nsp14 replication fork activity was hindered by the tomentosolic acid, timosaponin A-I, and shizukaol A with the binding affinity score of −9.2, −9.2, and −9.0 kcal/mol, respectively. The nsp15 endoribonuclease catalytic residues were inhibited potentially by limonin, 25-O-anhydrocimigenol 3-O-alpha-l-arabinopyranoside, and asperagenin posing strong binding affinity scores of −9.0, −8.8, and −8.7 kcal/mol, respectively. Computationally predicted potential phytochemicals for SARS-CoV-2 are known to possess various medicinal properties.

Design, Synthesis and Antibacterial Studies of 1,3,4‐Oxadiazole‐Fluoroquinolone Hybrids and Their Molecular Docking Studies

AbstractA series of novel hybrids built on fluoroquinolone skeleton were synthesized by introducing 1,3,4‐oxadiazole derivatives to the C‐7 site of ciprofloxacin or norfloxacin. In vitro antibacterial evaluation showed that hybrids 4 b–d (5‐(hydroxyphenyl)‐1,3,4‐oxadiazol‐2‐yl substituted ciprofloxacin) were an increased activity against Staphylococcus aureus, with a minimum inhibitory concentration (MIC) of ≤0.125 μg/mL, four times superior to the parent drug. Hybrids 4 b–e (4 e, 5‐(4‐(trifluoromethyl) phenyl)‐1,3,4‐oxadiazol‐2‐yl substituted ciprofloxacin) also exhibited significant activity against methicillin‐resistant S. aureus (MRSA), resistant to the parent drug. All the hybrids demonstrated a bactericidal effect on standard bacteria with the MBC value not exceeding four times of their corresponding MIC values. In time‐killing assays, 4 c demonstrated a superior bactericidal action in eradicating S. aureus and E. coli within 2 h, respectively, equipotent to ciprofloxacin. In the molecular docking study, hybrids 4 c exhibited a high binding affinity for type IV topoisomerase with a minimum binding energy of −10.2 kcal/mol.

Formation and characterization of furfuryl mercaptan-β-cyclodextrin inclusion complex and its thermal release characteristics

Abstract Furfuryl mercaptan has the aroma characteristics of coffee. However, it is unstable during storage of coffee brew and roasted coffee. In order to enhance the stability of furfuryl mercaptan, furfuryl mercaptan-β-cyclodextrin inclusion complex was synthesized using the precipitation method in this work. Fourier transform infrared spectroscopy, x-ray diffraction, and thermogravimetric analysis (TG) were used to characterize the resulting products. The interaction of furfuryl mercaptan with β-cyclodextrin was investigated by the molecular mechanics (MM) method. These changes in FTIR and XRD gave supporting evidence for the successful formation of furfuryl mercaptan-β-cyclodextrin inclusion complex. The TG results showed that the formation of furfuryl mercaptan-β-cyclodextrin inclusion complex could improve the thermal stability of furfuryl mercaptan and provide a long-lasting effect. The structure of furfuryl mercaptan-β-cyclodextrin inclusion complex with the minimum energy was obtained by MM2 calculation, and the minimum binding energy was –77.0 kJ mol−1 at –1.96 × 10–10 m.

Antibacterial, Docking, DFT and ADMET Properties Evaluation of Chalcone-Sulfonamide Derivatives Prepared Using ZnO Nanoparticle Catalysis.

IntroductionIn the present work, two novel compounds were synthesized using zinc oxide nanoparticles through green synthesis protocol. The zinc oxide nanoparticles catalyzed reactions were afforded good to excellent yields of the target compounds 76.3–98.6%.MethodologyThe synthesized compounds were characterized by UV-Vis, IR and NMR. The antibacterial activity of the synthesized compounds was screened against two Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus) and two Gram-negative bacteria (Escherichia coli and Salmonella typhimurium).Results and DiscussionThe synthesized compounds displayed potent activity against the bacterial strains. Among them, compound 8 showed strong activity against Bacillus cereus relative to the standard drug. On the other hand, compound 9 exhibited strong activity against Escherichia coli. The molecular docking study of the synthesized compounds was conducted to investigate their binding pattern with DNA gyrase and E. coli dihydropteroate synthase and all of them were found to have minimum binding energy ranging from –6.0 to −7.3 kcal/mol, and the best result achieved with compound 8 and 9.ConclusionThe findings of the in vitro antibacterial and molecular docking analysis demonstrated that the synthesized compounds have potential of antibacterial activity and can be further optimized to serve as a lead compound.

Identification of potent inhibitors of ATP synthase subunit c (AtpE) from Mycobacterium tuberculosis using in silico approach

ATP synthase subunit c (AtpE) is an enzyme that catalyzes the production of ATP from ADP in the presence of sodium or proton gradient from Mycobacterium tuberculosis (MTB). This enzyme considered an essential target for drug design and shares the same pathway with the target of Isoniazid. Thus, this enzyme would serve as an alternative target of the Isoniazid. The three dimensional (3D) model structure of the AtpE was constructed based on the principle of homology modeling using the Modeller9.16. The developed model was subjected to energy minimization and refinement using molecular dynamic (MD) simulation. The minimized model structure was searched against Zinc and PubChem database to determine ligands that bind to the enzyme with minimum binding energy using RASPD and PyRx tool. A total of 4776 compounds capable of bindings to AtpE with minimum binding energy were selected. These compounds further screened for physicochemical properties (Lipinski rule of five). All the compounds that possessed the desirable property selected and used for molecular docking analysis. Five (5) compounds with minimum binding energies ranged between ─8.69, and ─8.44 kcal/mol, less than the free binding energy of ATP were selected. These compounds further screened for the absorption, distribution, metabolism, excretion, and toxicity (ADME and toxicity) properties. Of the five compounds, three (ZINC14732869, ZINC14742188, and ZINC12205447) fitted all the ADME and toxicity properties and subjected to MD simulation and Molecular Mechanics Generalized Born and Surface Area (MM-GBSA) analyses. The results indicated that the ligands formed relatively stable complexes and had free binding energies, less than the binding energy of the ATP. Therefore, these ligands considered as prospective inhibitors of MTB after successful experimental validation.

In silico approach for enhancing innate lipid content of Yarrowia lipolytica, by blocking the acyl-CoA oxidase-1 enzyme, using various analogous compounds of lipids

Yarrowia lipolytica is used as a model in this study to screen the potential candidates for inflating the innate lipid content of the cell. This study focuses on reducing the lipid degradation that occurs by the β-oxidation process and discursively increasing the innate lipid content. Acyl-CoA oxidase-1, the primary and initial enzyme involved in the lipid degradation pathway, was selected as a target and blocked using various lipid analogous compounds. The blocking study was carried out using molecular docking and dynamic studies using computation tools. The largest active site pocket located around the Phe-394 amino acid of the target protein is taken as a site for docking. The molecular docking was performed for the selected compounds (citric acid, Finsolv, lactic acid, oxalic acid, Tween-80 and Triton X-100) and the docking results were compared with the outcome of the standard molecule (octadecatrienoic acid). Citric acid, Finsolv, Tween-80 and Triton X-100 were found to be the potential candidates for blocking the target molecule in the static condition using docking studies, revealing a minimum binding energy requirement than the standard molecule. They were further taken for a dynamics study using GROMACS software. The RMSD, RMSF, number of hydrogen bond interactions and radius of gyration of the complex molecules were studied in a dynamic approach for 100 ns. Citric acid has been found to be the potential hit compound to block acyl-CoA oxidase-1 enzyme with its maximum hydrogen interaction and minimum fluctuations. It also revealed out the minimum total energy requirement for the complex formation.

Synthesis, Identification, Computer-Aided Docking Studies, and ADMET Prediction of Novel Benzimidazo-1,2,3-triazole Based Molecules as Potential Antimicrobial Agents.

2-azido-1H-benzo[d]imidazole derivatives 1a,b were reacted with a β-ketoester such as acetylacetone in the presence of sodium ethoxide to obtain the desired molecules 2a,b. The latter acted as a key molecule for the synthesis of new carbazone derivatives 4a,b that were submitted to react with 2-oxo-N-phenyl-2-(phenylamino)acetohydrazonoyl chloride to obtain the target thiadiazole derivatives 6a,b. The structures of the newly synthesized compounds were inferred from correct spectral and microanalytical data. Moreover, the newly prepared compounds were subjected to molecular docking studies with DNA gyrase B and exhibited binding energy that extended from −9.8 to −6.4 kcal/mol, which confirmed their excellent potency. The compounds 6a,b were found to be with the minimum binding energy (−9.7 and −9.8 kcal/mol) as compared to the standard drug ciprofloxacin (−7.4 kcal/mol) against the target enzyme DNA gyrase B. In addition, the newly synthesized compounds were also examined and screened for their in vitro antimicrobial activity against pathogenic microorganisms Staphylococcus aureus, E. coli, Pseudomonas aeruginosa, Aspergillus niger, and Candida albicans. Among the newly synthesized molecules, significant antimicrobial activity against all the tested microorganisms was obtained for the compounds 6a,b. The in silico and in vitro findings showed that compounds 6a,b were the most active against bacterial strains, and could serve as potential antimicrobial agents.

Design of functional glycerol-based deep eutectic solvents as reaction media for enzymatic deacidification of high-acid rice bran oil

The effectiveness of deacidification technologies for high-acid rice bran oil (HRBO) are still one of the main challenges in the industrialization process of rice bran oil (RBO). A novel function of glycerol-based deep eutectic solvents (DESs) as an acyl acceptor in combination with lipases for enzymatic esterification of deacidification of HRBO was described in this study. The maximum deacidification efficiency of 92.38% was obtained under the optimized reaction conditions. Molecular docking simulation indicated that the minimum binding energy of Novozym 435 was lower than those of Lipozyme TL IM and Lipozyme RM IM, which might be one of the underlying mechanisms for its better performance. Additionally, γ-oryzanols, tocopherols and tocotrienols were retained in deacidified RBO. We are convinced that the reusability of biocatalyst and DESs systems provide an alternative strategy to design a facile, environmentally-friendliness DESs towards economic feasibility of applications and processes for oil-refined industries.

Modeling the interaction of thiozonide and atphase M.tuberculosis by the method of molecular docking

The mechanism of interaction of a new anti-tuberculosis drug thiosonide with a probable target of M. tuberculosis was studied. According to the data obtained, the most likely target with a thiozonide binding pocket is the subunit of bacterial ATP synthase, an enzyme that plays a key role in the processes of energy exchange in the cell, coupling the reaction of ATP synthesis/hydrolysis with transmembrane proton transfer. Original models of the three subunits of this enzyme (alpha, delta, and epsilon) were built. To simulate docking in silico, the AutoDock program version 4.2 was used, which is included in the MGL Tools version 1.5.6. It was shown that all three subunits have clusters with the minimum binding energies for the thiosinide molecule, and the epsilon subunit has two clusters with equal probabilities of being a thiosinide binding site.

Facile synthesis of some 5-(3-substituted-thiophene)-pyrimidine derivatives and their pharmacological and computational studies

A series of 5-(3-substituted-thiophene)-pyrimidine derivatives (3a-d) were synthesized via Knoevenagel condensation reaction in aq. ethanol using H2O2:HCl as a catalyst. Their pharmacological effects were evaluated. Analytical and spectroscopic methods confirmed the structures of the target molecules. The antibacterial activity studies revealed that compounds 3b and 3d exhibited the most effective zone of inhibition against bacterial strains E. coli and S. aureus, respectively. The in vitro cytotoxicity was carried out by MTT assay against MCF-7 cell line. The results showed excellent selectivity for all four compounds, among which the compound 3a exhibited remarkable cytotoxicity with a minimum cell viability range of 23.68 to 44.16%. The interaction of compounds with calf thymus DNA was determined using UV-absorption spectroscopy. The results confirmed that all the synthesized compounds interacted strongly with CT DNA through electrostatic or groove binding. In silico ADME-toxicology studies indicated that all the molecules under investigation are non-toxic with good oral bioavailability. The drug-likeness score indicated that they are suitable as drug-leads. In silico molecular docking the specified compound 3b bound with GlcN-6-P and P38 MAPk with a minimum binding energy of –7.9 and –6.4 kcal/mol, respectively. DFT study demonstrated that compound 3d was chemically and biologically more reactive due to less energy gap.

Structural, vibrational, electronic properties, hirshfeld surface analysis topological and molecular docking studies of N-[2-(diethylamino)ethyl]-2-methoxy-5-methylsulfonylbenzamide

The theoretical (Freebase, Cationic species) and experimental investigations on the molecular structural, spectroscopic characterization, and electronic properties of N2M5MB are reported. The most stable structure of the N2M5MB was analysed by employing Density Functional Theory (DFT) at different functional such as B3LYP, PBEPBE, TPSSTPSS and IEF-PCM (Freebase) and Cationic (B3LYP, IEF-PCM)/ 6–311++G (d,p) basis set level. The Potential Energy Scan (PES) analysis has been employed to investigate the conformational preference of the title molecule. The optimized molecular geometry, vibrational assignments (FT-IR, FT-Raman) of wavenumbers have been performed for freebase, cationic species (Gas, PCM) for the individual modes of vibration. The experimental UV-Vis absorption spectrum was obtained and compared with the simulated (Freebase, Cationic species) Time-Dependent (TD-DFT-M062X) method. The FMO's, electron-hole distributions, HOMA, FLU, Hirshfeld surface analysis, Electrostatic potential surface (ESP), Fukui functions, and topological parameters were discussed. Molecular docking studies were performed for the N2M5MB (ligand) into the active site of targeted proteins (1H22, 4DTL, 5OV9) which belong to AChE inhibitors with the minimum binding energy was detected.

Computational Screening of Natural Compounds for Identification of Potential Anti-Cancer Agents Targeting MCM7 Protein.

Minichromosome maintenance complex component 7 (MCM7) is involved in replicative licensing and the synthesis of DNA, and its overexpression is a fascinating biomarker for various cancer types. There is currently no effective agent that can prevent the development of cancer caused by the MCM7 protein. However, on the molecular level, inhibiting MCM7 lowers cancer-related cellular growth. With this purpose, this study screened 452 biogenic compounds extracted from the UEFS Natural Products dataset against MCM protein by using the in silico art of technique. The hit compounds UEFS99, UEFS137, and UEFS428 showed good binding with the MCM7 protein with binding energy values of −9.95, −8.92, and −8.71 kcal/mol, which was comparatively higher than that of the control compound ciprofloxacin (−6.50). The hit (UEFS99) with the minimum binding energy was picked for molecular dynamics (MD) simulation investigation, and it demonstrated stability at 30 ns. Computational prediction of physicochemical property evaluation revealed that these hits are non-toxic and have good drug-likeness features. It is suggested that hit compounds UEFS99, UEFS137, and UEFS428 pave the way for further bench work validation in novel inhibitor development against MCM7 to fight the cancers.

Molecular docking, modeling, semiempirical calculations studies and in vitro evaluation of new synthesized pyrimidin-imide derivatives

New pyrimidin-imide derivatives 2-7 were synthesized by a condensation reaction of 4,6-diphenylpyrimidin-2-amine 1 with different anhydrides. The synthesized compounds have been investigated and put under several studies suc as, in vitro and in silico techniques, Lipinski's rule of five (RO5), semiempirical (PM6) computational calculations in addition of some physicochemical parameters measurments to evaluate their biological effect against Penicillin-Binding Protein 3 (PBP3) from Escherichia coli. These studies revealed that the newly synthesized pyrimidin-imides have minimum binding energy and good affinity especialy for ligand molecule 5 which may be considered a promising inhibitor for the PBP3 protein. The structures of all newly derivatives were unambiguously confirmed by their elemental and spectral analyses IR, 1H NMR, 13C NMR, and MS.

Evaluation of electronic properties in different solvents, spectroscopic exposition (FT-IR, FT-Raman), and molecular docking studies of 5-Chloro-2-hydroxypyridine - insulysin inhibitor

In the current work, the experimental and theoretical reports on the upgraded geometrical structure, electronic and vibrational features of 5-chloro-2-hydroxypyridine are presented assigning B3LYP method with 6–311++G (d, p) basis set. The FT-IR and FT-Raman spectra of the heading compound were documented and the geometric parameters and wavenumbers were obtained and with scaled quantum mechanics, comprehensive vibrational assignments of wavenumbers using Potential Energy Distribution (PED) were evaluated. NBO studies was used to calculate the interaction energy and electron densities of donor and acceptor bonds. Various solvents were used to find HOMO-LUMO orbitals and band gap energy. Molecular Electrostatic Potential (MEP), Fukui functions, Mulliken charges, Electron Localisation Function (ELF) and Localised Orbital Locator (LOL) of the heading molecule were also inspected. Using the TD-DFT method and a number of solutions, the UV–Visible spectrum was explored. Additionally, drug likeness, environmental toxicity properties were analysed and molecular docking was accomplished so as to recognize the hydrogen bond lengths and minimum binding energy was determined.

Theoretical design and preparation research of molecularly imprinted polymers for steviol glycosides.

In this paper, a novel molecularly imprinted polymer (MIP) for specific adsorption of steviol glycosides was designed, and the imprinting mechanism of self-assembly system between template and monomers was clearly explored. Firstly, steviol (STE) was chosen as dummy template, and the density functional theory (DFT) at B3LYP/6-31 + G (d, p) level was used to select monomers, imprinting molar ratios, solvents, and cross-linking agents. The selectivity to five steviol glycosides was also calculated. Importantly, reduced density gradient (RDG) theory combined with atom in molecules (AIM) and infrared spectrum (IR) was applied to investigate the bonding situation and the nature of noncovalent interaction in self-assembly system. The theoretical designed results showed that the template which interacts with acrylic acid (AA) has the minimum binding energy, and the complex with the molar ratio of 1 : 4 has the most stable structure. Toluene (TL) and ethylene glycol dimethacrylate (EGDMA) were chosen as the optimal solvent and cross-linking agent, respectively. Five hydrogen bonds formed in the self-assembly system are the key forces at the adsorption sites of MIPs through the RDG and AIM analyses. The MIPs were synthesized by theoretical predictions, and the results showed that the maximum adsorption capacity towards dulcoside A is 26.17mg/g. This work provided a theoretical direction and experimental validation for deeper researches of the MIPs for steviol glycosides. In addition, the method of RDG theory coupled with AIM and IR also could be used to analyze other imprinting formation mechanisms systematically.