•Synthesis and design of new heterocyclic compounds based on quinolones-L-alaninate.•The chemical structure of the prepared compounds was confirmed by NMR spectroscopy and mass spectra ...analysis.•Antimicrobial and antifungal activities of the quinolone amino derivatives were studied.•Quantum chemical calculations explained the observed selectivity of the N-alkylation reaction.•Docking and molecular dynamic simulations were used to explain the experimental biological activity results.
A new selective synthesis of novel quinoline carboxamides was developed by the N-alkylation reaction of methyl (2-oxo-1,2- dihydroquinolin-4-yl)-l-alaninate via phase transfer catalysis in a basic medium at room temperature. The compounds were obtained in excellent yields (70–90%) and characterized by 1H, 13CNMR spectroscopy and mass spectra. In addition, theoretical studies at B3LYP/6–311G(d,p) level were carried out to explain the observed selectivity of the N-alkylation reaction of compound 2. The biological activities of the synthesized compounds were studied using some bacterial and fungal strains. The results show that compounds 3h and 3i exhibit stronger antibacterial activity against Bacillus subtilis and Staphyloccocus aureus. Compound 3e showed high antifungal activity against Candida Albicans compared to other substituted quinoline carboxamides. Molecular docking and molecular dynamics studies were also carried out to investigate the binding affinities of some compounds with the target proteins, and the results were in good correlation with the experimental findings.
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In this work, four different oxygen functionalized ionic liquids, 1-(3-hydroxypropyl)-3-methylimidazolium chloride,OHC3mImCl, 1-(3-hydroxypropyl)-3-ethylimidazolium chloride OHC3eImCl, ...1-(2-oxobutyl)-3-methylimidazolium chloride, C2OC2mImCl and 1-(4-hydroxy-2-oxobutyl)-3-methylimidazolium chloride, OHC2OC2mImCl were synthesized in liquid state at room temperature. Detailed physico-chemical characterisation (density, viscosity and conductivity) supported with computational simulations for pure ionic liquid and their aqueous solutions were performed. Based on these examinations, interactions in pure ionic liquids and interactions between water and synthesized ionic liquids were discussed.
We present a state-of-the-art virtual screening workflow aiming at the identification of novel CC chemokine receptor 7 (CCR7) antagonists. Although CCR7 is associated with a variety of human ...diseases, such as immunological disorders, inflammatory diseases, and cancer, this target is underexplored in drug discovery and there are no potent and selective CCR7 small molecule antagonists available today. Therefore, computer-aided ligand-based, structure-based, and joint virtual screening campaigns were performed. Hits from these virtual screenings were tested in a CCL19-induced calcium signaling assay. After careful evaluation, none of the
hits were confirmed to have an antagonistic effect on CCR7. Hence, we report here a valuable set of 287 inactive compounds that can be used as experimentally validated decoys.
In this research, the influence of dye structure and dyeing temperature on the adsorption of acid dyes onto polyamide
6 knitwear (PA 6) was studied. Three acid dyes with different amounts of ...sulphonic groups, namely C. I. Acid Red 88,
C. I. Acid Red 14, and C. I. Acid Red 18 were used. Dyeing was performed in a Launder-ometer apparatus at 40°C and
60°C, at pH 4. The samples were taken out of the apparatus at different time intervals. The results showed that both dye
structure and dyeing temperature affected the adsorption of acid dyes onto PA 6 knitwear. The rate and quantity of
adsorption increased with an increase in dyeing temperature and a decrease in the number of sulphonic groups in dyes.
The changes in hydration structure of β-alanine and L-histidine through dipeptide formation were studied and discussed from experimentally measured values of densities, viscosities and computational ...investigations of amino acids diluted aqueous solutions, β-alanine and L-histidine, and the final dipeptide, L-carnosine over the temperature range from 283.15 K to 313.15 K. The apparent molar volume (Vϕ), apparent molar volume at infinite dilution (Vϕo), Masson's experimental slope (Sv), limiting apparent molar expansibility, (Eϕo), Hepler's coefficient, hydration number, and viscosity B coefficient have been evaluated using the experimental density and viscosity values. The formation of the peptide bond has been examined in terms of water structuring nature around dipeptide and starting amino acids, and how it is linked with dipeptide self-interactions. Also, L-carnosine solubility in water was determined, as well as the thermal decomposition of the investigated compounds was examined by simultaneous thermogravimetric (TG) and DSC measurement. For the evaluation of their decomposition, the data obtained by coupled TG–mass spectrometric (MS) measurements were used.
•L-carnosine solubility in water was determined.•TG-MS analysis showed almost the same main decomposition products and ion fragment distribution of three examined compounds.•L-carnosine have the more pronounced structure making comparing to L-histidine and β-alanine.•The entropy increase of L-carnosine due to dipeptide self-interaction and release of electrostricted water.
Based on data analyzed from volumetric, viscosimetric measurements and computational simulations, caffeine hydration and aggregation properties in aqueous solutions were compared with caffeine ...properties in the presence of ATP. The experimental values of the apparent molar volume (Vϕ), apparent molar volume at infinite dilution (Vϕo), Masson's experimental slope (Sv), the apparent molar volume of transfer (ΔtrVϕo), limiting apparent molar expansibility, (Eϕo), hydration number, viscosity B coefficient, thermodynamics parameters of viscous flow were calculated in the temperature range from T = (283.15 to 313.15) K. For the additional investigation of the caffeine hydration properties, the molecular dynamics (MD) simulations, the radial distributive functions (RDFs) and spatial distribution functions (SDFs) were performed. Reduced caffeine hydration and pronounced self-aggregation in the ATP presence are linked to its dehydration effect on caffeine molecules. These results point out the ATP negative effects on caffeine, due to undesirable process of active molecule self-aggregation leading to the reduce bioavailability in the biological systems.
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•The influence of ATP on hydration and self-aggregation properties of caffeine was examined.•The presence of ATP reduces caffeine hydration and promotes its self−aggregation.•The dehydration effect of caffeine was pronounced by ATP.•The local supersaturation of caffeine is the self−aggregation driving force.
Razvili smo prototip vzporednega algoritma za in silico molekulsko sidranje, ki omogoča izrabo heterogenih računalniških arhitektur in posledično računsko moc modernih osebnih računalnikov in ...superračunalniških gruč. Uporabili smo programsko ogrodje OpenCL, ki podpira strojno opremo različnih proizvajalcev. Vzporedni algoritem išče optimalno pozo oziroma konformačijo molekule v rečeptorskem mestu beljakovine, kar imenujemo molekulsko sidranje, pri tem pa uporablja empirično čenilno funkčijo za očenjevanje rešitev. Rešitev smo preizkusili na več beljakovinskih kompleksih in dobljene rezultate primerjali z referenčno implementačijo programa CmDočk. Analizirali smo optimalnost dobljenih konformačij molekul in hitrost algoritma. Vzporedni algoritem izkazuje izrazito hitrejše delovanje na grafičnih pročesnih enotah. Za učinkovitejšo izrabo strojne opreme in večje pohitritve je treba algoritem dodatno optimizirati ter izpopolniti čenilno funkčijo za pridobitev ustreznih vezavnih konformačij ligandov. Programska koda bo dostopna na https://gitlab.čom/Jukič/čmdočk/.
In this study, a quantitative structure‐activity relationship (QSAR) model of anticancer activity against myeloid cell leukemia 1 (Mcl‐1) for a series of 41 tricyclic indole diazepinone derivatives ...is established. Three different modeling methods, multiple linear regression (MLR), partial least square (PLS), and artificial neural network (ANN) are investigated to perform a QSAR model with significant predictiveness. A clustering method is also used for dividing all compounds into training and external test (ET) sets. Component principal analysis is used to eliminate the redundancy between descriptors. The accuracy and predictability of the proposed models are proven by comparing their key statistical terms. The good results obtained with the internal and external validations (EV) show that the proposed models can predict high‐performance activities and that the selected descriptors are pertinent. This model is also validated using internal validation (IV), mainly using cross‐validation (leave‐many‐out (LMOCV)). The applicability domain (AD) is identified. Based on the SAR map analysis, a novel Mcl‐1 inhibitor with a good predicted activity using the best model is proposed, the interaction of the designed compound with the binding site of Mcl‐1 protein is evaluated and its docking score is found high.
Taking into account the crucial role of Myeloid cell leukemia 1(Mcl‐1) as an anti‐apoptotic protein and the resistance difficulties caused by its upregulation, the authors have tried in this work to use chemoinformatic, particularly the quantitative structure‐activity relationship approach (QSAR) to find inhibitors specific to Mcl‐1 protein.
Seven title compounds 12a–g and the (S)-prolinate analogue 13 were prepared in five steps from 2-nitrobenzoic acid (7). Reduction of the nitro group followed by derivatization of the so formed ...anilines 14 gave the N-alkyl-(15a–c), N-acyl-(16a,b and 19), and N-vinyl derivative 20. NMR spectra of (S)-alanine and (S)-proline derived compounds 12, 13, 14–16, 19, and 20 exhibited two sets of signals corresponding to pairs of conformational diastereomers. The free energy barriers of rotation, ΔG ‡ 298 = 82–86 kJ mol–1, were determined by 1H NMR for 12a, 12d, 12f, and 12g and evaluated by DFT calculations.
Gold is a valuable metal that can be dissolved with common household chemicals as reported by Timo Repo et al. in their Research Article (e202117587). By applying catalytic iodine, aqueous hydrogen ...peroxide and 2‐mercaptobenzimidazole, gold promptly dissolves in ethanol. Catalytic reactions and environmentally benign solvents and reagents are the basis for sustainable development and a gateway to a greener future of precious metals recycling.
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