Indolyl-Derived 4H-Imidazoles: PASE Synthesis, Molecular Docking and In Vitro Cytotoxicity Assay

The strategy of the nucleophilic substitution of hydrogen (SNH) was first applied for the metal-free C-H/C-H coupling reactions of 4H-imidazole 3-oxides with indoles. As a result, a series of novel bifunctional azaheterocyclic derivatives were obtained in yields up to 95%. In silico experiments on the molecular docking were performed to evaluate the binding possibility of the synthesized small azaheterocyclic molecules to the selected biotargets (BACE1, BChE, CK1δ, AChE) associated with the pathogenesis of neurodegenerative diseases. To assess the cytotoxicity for the synthesized compounds, a series of in vitro experiments were also carried out on healthy human embryo kidney cells (HEK-293). The leading compound bearing both 5-phenyl-4H-imidazole and 1-methyl-1H-indole moieties was defined as the prospective molecule possessing the lowest cytotoxicity (IC50 > 300 µM on HEK-293) and the highest binding energy in the protein–ligand complex (AChE, −13.57 kcal/mol). The developed compounds could be of particular interest in medicinal chemistry, particularly in the targeted design of small-molecule candidates for the treatment of neurodegenerative disorders. © 2023 by the authors.Ministry of Education and Science of the Russian Federation, Minobrnauka: 075-15-2022-1118, W03.31.0034; Russian Science Foundation, RSF: 20-73-10077The chemical design, synthesis and characterization of indolyl-derived 4H -imidazoles and in vitro studies were supported by the Russian Science Foundation (Project # 20-73-10077). The in silico studies were supported by the Ministry of Science and Higher Education of the Russian Federation (Ref. # 075-15-2022-1118, dated 29 June 2022). The synthesis of starting 4H -imidazole N -oxide substrates was supported by the Ministry of Science and Higher Education of the Russian Federation (Project # 14.W03.31.0034)

Gas-dynamic stage of laser plasma evolution : 2D simulation

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Solution of two‐dimensional multi‐interface Stefan problem by the method of dynamic adaptation

In the present work a method of numerical solution of multi‐interface two‐dimensional Stefan problem with explicit tracking of the interfaces in the domains of arbitrary form is considered. The method is based on the idea of dynamic adaptation of the calculated grid by means of transition to an arbitrary non‐stationary coordinate system. The coordinate system transformation is controlled by the solution. The method is described by using the example of the problem that is typical for treatment of materials with concentrated energy fluxes. Dvimačio daugiansluoksnio stefano uždavinio sprendimas dinaminio adaptavimo metodu Santrauka Straipsnyje nagrinejamas dvimačio daugiasluoksnio Stefano uždavinio adaptyvus sprendimo algoritmas. Naudojamas išreikštinis fronto skaičiavimo algoritmas, leidžiantis rasti bet kokios formos kontūrus. Remiantis dinaminiu adaptavimo algoritmu, fizine sritis yra atvaizduojama i fiksuota skaičiavimo sriti. Transformacijos atvaizdavimas adaptyviai priklauso nuo pačio uždavinio sprendinio. Bendrasis metodas pateiktas dvieju medžiagu saveikos uždaviniui. Naujojo algoritmo efektyvumas iliustruojamas skaičiavimo eksperimento rezultatais. First Published Online: 14 Oct 201

Laser plasma formation in metals vapour : kinetic approach

The break-down of metals vapour (Al, Cu) are simulated near the break-down threshold values of laser radiation. The approximations of collision-radiation model are used, including the detail kinetics of exited states with radiation and collision transitions, step-by-step ionisation process, unexitation and recombination. Energy balance is based on two-temperature approximation : for electrons and for heavy particles. It is shown that the particles concentration in exited states and plasma species composition differ rather from Saha-Boltzmann's distribution. Strong dependence of the break-down threshold intensity on initial temperature of neutral and charged particles is shown