卷 14, 编号 4 (2024)

One of the directions in the development of organic chemistry is the synthesis of biologically active compounds, including those with bactericidal activity, based on available petrochemical raw materials. In order to expand the library of bioactive compounds containing a 1,3-dioxacyclane fragment, the synthesis of derivatives of 5-acyl-5-isopropyl-1,3-dioxane – 1-(5-isopropyl-1,3-dioxane-5-yl)ethanol and (5-isopropyl-1,3-dioxane-5-yl)ethyl phenyl carbamate was carried out. The effect of synthesized compounds containing a 1,3-dioxacyclane fragment on the growth of strains of gram-negative and gram-positive bacteria, lower fungi Candida albicans was studied. It was found that 2-methyl-2-ethyl-4-chloromethyl-1,3-dioxolane, containing a chloromethyl group, has an antimicrobial effect against gram-positive and gram-negative test cultures and weak antifungal activity (minimum inhibitory concentration is 100 μg/mL) against lower fungi Candida albicans. 1-(5-Isopropyl-1,3-dioxan-5-yl)ethanol exhibits antifungal activity (minimum inhibitory concentration is 2 μg/mL) and sharply reduces antimicrobial activity against Klebsiella pneumonia, Staphylococcus aureus, Enterobacter aerogenes (minimum inhibitory concentration is 100 μg/mL), in contrast to the structurally similar 2-methyl-2-ethyl-4-hydroxymethyl-1,3-dioxolane, which did not show similar properties. 5-Acyl-5-isopropyl-1,3-dioxane, containing a carbonyl group in its structure, showed antimicrobial activity (minimum inhibitory concentration is 25 μg/mL) against gram-negative test cultures, with the exception of Pseudomonas aeruginosa. Heterocycles (2-methyl-2-ethyl-4-chloromethyl-, 2-isobutyl-2,4-dimethyl-, 2-methyl-2-isobutyl-4-chloromethyl- and 2-methyl-2-isobutyl-4-hydroxymethyl-1,3-dioxolane) at concentrations up to 100 μg/mL did not inhibit the vital activity of the studied bacteria and lower fungi. The results obtained show the prospect of continuing the search for new antimicrobial and antifungal drugs of the series of 1,3-dioxacycloalkanes, the structure of which is fundamentally different from the known antibacterial drugs.

The present study examines reaction products in the solution of antibiotic cefotaxime with succinic anhydride, maleic anhydride copolymer, and dialdehyde wheat starch. The reaction of cefotaxime with succinic anhydride is shown to produce succinamide; to maleic anhydride copolymer, cefotaxime is likely to bind via noncovalent intermolecular interactions. An azomethine derivative of oxidized polysaccharide with cefotaxime was found to form; the molar ratio of initial glucosidic units in starch, unreacted dialdehyde units, and those bonded to cefotaxime through the azomethine linkage is 0.204:0.606:0.19. Drug release from the obtained matrix form was studied in different biorelevant media (saline, phosphate buffer, and Tris-HCl buffer). The amount of cefotaxime released in ten hours was found to approach 100%. Its release proceeds in two phases. In the first phase (1–2 h), 35 (pH 7.14) to 70% (pH 7.4–8.0) of the drug substance is released into the solution, followed by a significant decrease in the release rate. The processing of kinetic data using the first-order and Higuchi equations revealed consistency with both models. The obtained rate constants increase in proportion to the solution pH. It is assumed that first, the azomethine bond hydrolysis occurs with the release of cefotaxime molecules from the polymer matrix; then, the macromolecules of oxidized starch residing on the surface are dissolved; due to an increase in the viscosity of the solution layer surrounding the conjugate particle, the hydrolysis rate decreases. In general, cefotaxime release from the conjugate proceeds as a pseudo-first-order reaction accompanied by diffusion processes.

The development of new promising materials of three-dimensional structure from available bioresorbable, biointegrable and biocompatible polymers is in demand and relevant in connection with the intensive development of regenerative medicine. In this work, hydrogels of the grafted copolymers of methyl methacrylate/butyl acrylate onto a mixture of collagen and pectin were obtained during photocatalysis in the presence of a complex oxide RbTe1.5W0.5O6. The characteristics of the synthesis products were obtained by gel penetrating chromatography, elemental analysis, electron microscopy, and biological biocidality tests. The collagen content in an amount of less than 40%, the microstructure of the polymer in the form of a fine-mesh, and the biocidity of the sample films were established. The polymer product was identified on the catalyst surface after the separation of the oxide powder from the aqueous dispersion. The main advantage of such materials is the unique combination of properties of their components assembled into a specific structure. The advantages of the obtained material include, among other things, the environmental advantage of the initial components - natural renewable raw materials: collagen was isolated from cod processing waste, pectin from fruit and vegetable processing waste.