Coronavirus disease (COVID-19) is one of the greatest challenges of the twentieth century. Recently, in silico tools help to predict new inhibitors of SARS-CoV-2. In this study, the new compounds ...based on the remdesivir structure (12 compounds) were designed.Background and purposeCoronavirus disease (COVID-19) is one of the greatest challenges of the twentieth century. Recently, in silico tools help to predict new inhibitors of SARS-CoV-2. In this study, the new compounds based on the remdesivir structure (12 compounds) were designed.The main interactions of remdesivir and designed compounds were investigated in the 3CLpro active site. The binding free energy of compounds by the MM-GBSA method was calculated and the best compound (compound 12 with the value of -88.173 kcal/mol) was introduced to the molecular dynamics simulation study.Experimental approachThe main interactions of remdesivir and designed compounds were investigated in the 3CLpro active site. The binding free energy of compounds by the MM-GBSA method was calculated and the best compound (compound 12 with the value of -88.173 kcal/mol) was introduced to the molecular dynamics simulation study.The simulation results were compared with the results of protein simulation without the presence of an inhibitor and in the presence of remdesivir. Additionally, the RMSD results for the protein backbone showed that compound 12 in the second 50 nanoseconds has less fluctuation than the protein alone and in the presence of remdesivir, which indicates the stability of the compound in the active site of the Mpro protein. Furthermore, protein compactness was investigated in the absence of compounds and the presence of compound 12 and remdesivir. The Rg diagram shows a fluctuation of approximately 0.05 A, which indicates the compressibility of the protein in the presence and absence of compounds. The results of the RMSF plot also show the stability of essential amino acids during protein binding.Findings/ResultsThe simulation results were compared with the results of protein simulation without the presence of an inhibitor and in the presence of remdesivir. Additionally, the RMSD results for the protein backbone showed that compound 12 in the second 50 nanoseconds has less fluctuation than the protein alone and in the presence of remdesivir, which indicates the stability of the compound in the active site of the Mpro protein. Furthermore, protein compactness was investigated in the absence of compounds and the presence of compound 12 and remdesivir. The Rg diagram shows a fluctuation of approximately 0.05 A, which indicates the compressibility of the protein in the presence and absence of compounds. The results of the RMSF plot also show the stability of essential amino acids during protein binding.Supported by the theoretical results, compound 12 could have the potential to inhibit the 3CLpro enzyme, which requires further in vitro studies and enzyme inhibition must also be confirmed at protein levels.Conclusion and implicationsSupported by the theoretical results, compound 12 could have the potential to inhibit the 3CLpro enzyme, which requires further in vitro studies and enzyme inhibition must also be confirmed at protein levels.
Background
Invasive ductal carcinoma (IDC) is the most common type of breast cancer so its early detection can lead to a significant decrease in mortality rate. However, prognostic factors for IDC ...are not adequate and we need novel markers for the treatment of different individuals. Although positron emission tomography and magnetic resonance imaging techniques are available, they are based on morphological features that do not provide any clue for molecular events accompanying cancer progression. In recent years, “omics” approaches have been extensively developed to propose novel molecular signatures of cancers as putative biomarkers, especially in biofluids. Therefore, a mass spectrometry-based metabolomics investigation was performed to find some putative metabolite markers of IDC and potential metabolites with prognostic value related to the estrogen receptor, progesterone receptor, lymphovascular invasion, and human epidermal growth factor receptor 2.
Methods
An untargeted metabolomics study of IDC patients was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The multivariate principal component analysis by XCMS online built a model that could separate the study groups and define the significantly altered m/z parameters. The most important biological pathways were also identified by pathway enrichment analysis.
Results
The results showed that the significantly altered metabolites in IDC serum samples mostly belonged to amino acids and lipids. The most important involved pathways included arginine and proline metabolism, glycerophospholipid metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis.
Conclusions
Significantly altered metabolites in IDC serum samples compared to healthy controls could lead to the development of metabolite-based potential biomarkers after confirmation with other methods and in large cohorts.
Benzothiazole derivatives are essential intermediates in synthesizing a wide variety of medical and pharmaceutical compounds, and there is a great demand for a simple and efficient method to ...synthesize benzothiazoles under mild reaction conditions. Organic electrosynthesis as an energy-efficient process represents an environmentally benign and safer method than traditional methods for organic synthesis. Herein, we present bromine-free and straightforward synthesis of 2-amino benzothiazole derivatives via the reaction of aniline derivatives and ammonium thiocyanate using electrosynthesis in the presence of sodium bromide both as an electrolyte and as a brominating agent at room temperature in isopropyl alcohol (i-PrOH) as a solvent. The reaction of ammonium thiocyanate via C–H thiolation routes, using various aniline derivatives, resulted in a simple, green, and bromine-free synthesis of 2-amino benzothiazole in moderate to good yields under mild reaction conditions. Riluzole drug can be produced using the same procedure in moderate yields.
Backgound: Exploring potent compounds is critical to generating multi-target drug discovery. Hematin crystallization is an important mechanism of malaria.
A series of chloroquine analogues were ...designed using a repositioning approach to develop new anticancer compounds. Protein-ligand interaction fingerprints and ADMET descriptors were used to assess docking performance in virtual screenings to design chloroquine hybrid β-hematin inhibitors. A PLS algorithm was applied to correlate the molecular descriptors to IC50 values. The modeling presented excellent predictive power with correlation coefficients for calibration and cross-validation of r2 = 0.93 and q2 = 0.72. Using the model, a series of 4-aminoquinlin hybrids were synthesized and evaluated for their biological activity as an external test series. These compounds were evaluated for cytotoxic cell lines and β-hematin inhibition.
The target compounds exhibited high β-hematin inhibition activity and were 3-9 times more active than the positive control. Furthermore, all the compounds exhibited moderate to high cytotoxic activity. The most potent compound in the dataset was docked with hemoglobin and its pharmacophore features were generated. These features were used as input to the Pharmit server for screening of six databases.
The compound with the best score from ChEMBL was 2016904, previously reported as a VEGFR-2 inhibitor. The 11 compounds selected presented the best Gold scores with drug-like properties and can be used for drug development.
The 3D structure of vitamin P, an important bioflavonoid, has been studied in solution by 2D NMR spectroscopy and QM calculations.
Rutin, vitamin P, was extracted from
Salvia macrosiphon and ...identified by
1H,
13C,
1H–
1H COSY, HMQC, and HMBC spectroscopy. In parallel, density functional theory (DFT) using B
3LYP functional and split-valance 6-311G∗∗ basis set has been used to optimize the structures and conformers of rutin. Also experimental and theoretical methods have been used to correlate the dependencies of
1
J,
2
J, and
3
J involving
1H and
13C on the C5″–C6″ (
ω), C6″–O6″ (
θ), and C1‴–O6″ (
φ) torsion angles in the glycosidic moiety. New Karplus equations are proposed to assist in the structural interpretation of these couplings.
3
J
HH
depends mainly on the C–C (
ω) torsion angle, as expected, and
2
J
HH
values depend on both C–C (
ω) and C–O (
θ) torsions.
1
J
CH
values within hydroxymethyl fragments were also examined and found to depend on r
CH, which is modulated by specific bond orientation and stereoelectronic factors. In all calculations solvent effects were considered using a polarized continuum model (PCM).
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► Synthesis and IR, NMR and X-ray crystallographic data for naltrexone and oxycodone. ► Optimization of their structures and obtaining calculated IR, Raman and NMR spectra. ► ...Comparison between experimental and computational molecular parameters. ► Comparison between observed and computed IR,
1H NMR and
13C NMR spectra.
In this work, two important opioid antagonists, naltrexone and oxycodone, were prepared from thebaine and were characterized by IR,
1H NMR and
13C NMR spectroscopy. Moreover, computational NMR and IR parameters were obtained using density functional theory (DFT) at B3LYP/6–311++G** level of theory.
Complete NMR and vibrational assignment were carried out using the observed and calculated spectra. The IR frequencies and NMR chemical shifts, determined experimentally, were compared with those obtained theoretically from DFT calculations, showed good agreements. The RMS errors observed between experimental and calculated data for the IR absorptions are 85 and 105
cm
−1, for the
1H NMR peaks are 0.87 and 0.17
ppm and for those of
13C NMR are 5.6 and 5.3
ppm, respectively for naltrexone and oxycodone.
In this study, Pd nanoparticles encapsulated in the copper‐based mesoporous metal–organic framework (Cu 2 (BDC) 2 DABCO) and used as a reusable heterogeneous catalyst to establish a method for the ...direct benzylation of carboxylic acids through C‐H (sp 3 ) bond activation. The catalyst structure was characterized by scanning electron microscope (SEM), transmission electron microscopy (TEM), X‐ray diffraction (XRD), Brunauer–Emmett–Teller (BET), and inductively coupled plasma (ICP). This catalyst showed high catalytic activity, selectivity, and good functional group tolerance for the direct benzylation of carboxylic acids.
This research evaluated the proteolytic activity of Iranian and commercial probiotic strains (e.g., Bifidobacterium lactis, Lactobacillus acidophilus, and Lactobacillus casei) in yoghurt during 28 ...days of storage. Water-soluble peptides were extracted using high-speed centrifugation. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods were used to evaluate the bioactive activities of water-soluble peptide extract (WSPE). Antimutagenic and antibacterial activity against Staphylococcus aureus was investigated using the Ames test and agar gel diffusion method, respectively. There was a direct relationship between formation of bioactive peptides and degree of proteolysis. There was a significant difference between the probiotic and control samples. S. thermophilus + L. bulgaricus + Iranian strain of B. lactis had the highest antioxidant, antimutagenic and antibacterial activities. Therefore, Iranian B. lactis has a high potential for producing bioactive peptides having health benefits in commercial foods such as yoghurt, novel products and therapeutic peptides.
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The C-N bond of carboxamides is extremely stable under most conditions. The present study reveals an unconventional approach to the transamidation of primary amides using DCID as C-N ...bond activator. DCID alone mediates the reactions and no additional metal catalyst is required. The method exhibits broad scope and secondary and tertiary amide synthesized in good yield. The chemical structures of the intermediate 3 and all-synthesized compounds were confirmed by comparison of melting point with literature and NMR spectra.
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