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Twelve new [alpha],[omega]-bis[(3,5-dimethylpyrazol-4-yl)methylsulfanyl]alkanes linked by alkyl, diethyl sulfide, and triethyl dioxide spacers were prepared by the multicomponent reaction of acetylacetone, formaldehyde, [alpha],[omega]-dithiols, and monosubstituted hydrazines. Testing of these products for inhibition of [alpha]-amylase enzyme in vitro showed that bis(N-methylpyrazolylmethylsulfanyl)ethane 4a inhibits the enzyme by the competitive mechanism. Meanwhile, the water-soluble adduct of bis(isoxazolylmethylsulfanyl)ethane 2 with HC1 (2 * HCl) is a noncompetitive inhibitor. The molecular docking results attest to high complementarity between the test molecules and the enzymes such as [alpha]-amylases from Aspergillus niger and human pancreas. Bis-pyrazole compounds 1, 1 * HCl, and 4a and bis-isoxazole compounds 2 and 2 * HCl positioned in the active site of both a-amylases form two closely spaced clusters. For all cases, the bioactive conformations of the modeled ligands were identified, demonstrating high affinity of the bis-azoles (1, 1 * HCl, 2, 2 * HCl,4a) to the enzymes. Hydrogen bonds stabilizing their position in both a-amylases active sites were identified. Key words: bis-azoles, a-amylase, molecular docking, scaffold. Nous avons préparé douze nouveau* [alpha],[omega]-bis[(3,5-diméthylpyrazol-4-yl)méthylsulfonyl]alcanes reliés par des espaceurs alkyle, diéthylsulfure et triéthyldioxyde par réaction à composants multiples entre l'acétylacétone, le formaldéhyde, des [alpha],[omega]-dithiols et des hydrazines monosubstituées. L'évaluation de ces produits dans des tests d'inhibition in vitro d'une enzyme [alpha]-amylase a montré que l'inhibition de l'enzyme par le bis(N-méthylpyrazolylméthylsulfanyl)éthane 4à procède par un mécanisme compétitif. Cependant, l'adduit hydrosoluble du bis(isoxazolylméthylsulfanyl)éthane 2 avec HCl (2 * HCl) est un inhibiteur non compétitif. Les résultats d'amarrage moléculaire révèlent une forte complémentarité entre les molécules à l'essai et les enzymes telles que les a-amylases d'Aspergillus niger et du pancréas humain. Les composés bis-pyrazole 1,1 * HCl et 4a et les composés bis-isoxazole 2 et 2 * HCl positionnés dans le site actif des deu* [alpha]-amylases forment deux agrégats étroitement espacés. Dans tous les cas, nous avons trouvé des conformations bioactives des ligands modélisés, ce qui témoigne de la forte affinité des bis-azoles (1, 1 * HCl, 2, 2 * HCl, 4a) pour ces enzymes. Nous avons notamment relevé des liaisons hydrogène stabilisant leur positionnement dans les sites actifs des deux a-amylases. [Traduit par la Rédaction] Mots-clés: bis-azoles, [alpha]-amylase, amarrage moléculaire, structure de base., Introduction Currently, the therapy of type 2 diabetes mellitus accompanied by visceral adiposity implies the simultaneous pharmacological action on both pathogenesis mechanisms. (1-4) The modern concept of the therapy is [...]

Tubular bones are layered waveguide structures composed of soft tissue, cortical and porous bone tissue, and bone marrow. Ultrasound diagnostics of such biocomposites are based on the guided wave excitation and registration by piezoelectric transducers applied to the waveguide surface. Meanwhile, the upper sublayers shield the diseased interior, creating difficulties in extracting information about its weakening from the surface signals. To overcome these difficulties, we exploit the advantages of the Green's matrix-based approach and adopt the methods and algorithms developed for the guided wave structural health monitoring of industrial composites. Based on the computer models implementing this approach and experimental measurements performed on bone phantoms, we analyze the feasibility of using different wave characteristics to detect hidden diagnostic signs of developing osteoporosis. It is shown that, despite the poor excitability of the most useful modes associated with the diseased inner layers, the use of the improved matrix pencil method combined with objective functions based on the Green's matrix allows for effective monitoring of changes in the elastic moduli of the deeper sublayers. We also note the sensitivity and monotonic dependence of the resonance response frequencies on the degradation of elastic properties, making them a promising indicator for osteoporosis diagnostics. [ABSTRACT FROM AUTHOR]

Surface and pseudo-surface acoustic plane waves generated in two- and three-layer AlN/Diamond and AlN/Diamond/γ-TiAl structures by a point electric source are analyzed in the mathematical framework based on the Green's matrix integral representation and guided wave asymptotics derived using the residue technique. The attention is focused on the effect of pseudo-surface-to-surface wave degeneration at certain discrete values of h/λ (h is the thickness of the piezoelectric layer and λ is the wave-length). Earlier such optimal ratios were discovered and experimentally verified for the first pseudo-surface (Sezawa) wave mode in the AlN/Diamond structure. The present research reveals this effect for higher modes as well as examines its manifestation for three-layer structures with different diamond-to-AlN thickness ratios H/h. [ABSTRACT FROM AUTHOR]