Vol 24, No 10 (2021)

The rapid increase in the incidence of multidrug-resistant pathogens poses an important task for the scientific community to find new ways to combat such pathogens. This increase is due to the widespread use of antibiotics of the main pharmacological groups for the treatment of infectious diseases against the backdrop of the ongoing COVID-19 epidemic. One of the promising directions in this area is bacteriophages due to their effectiveness against resistant pathogens and safety of use. Nevertheless, bacteriophages have a number of limitations that hinder their widespread use. In this regard, studies of endolysins - enzymes synthesized at the end of the lytic cycle of bacteriophages and destroying the bacterial cell wall - are being increasingly actively pursued. This article describes the characteristics of endolysins, their classification and advantages in comparison with antibiotics and bacteriophages. The descriptions of research carried out in the world in the field of obtaining endolysin preparations are given. Developments for the production of mono-and combined endolysins for the treatment of a number of bacterial infections are described. The effectiveness of this approach for the treatment of infections, including those caused by multidrug-resistant pathogens, and the prospects for further work in this direction are shown.

The aim of the study. To evaluate the anticholinesterase activity of 3-formylchromine derivatives in experimental Alzheimer's disease in rats. Material and methods. The work was performed on male Wistar rats that were modeled for Alzheimer's disease by injecting the fragment AB1-42 into the CA1 part of the hippocampus. The test-compounds and the reference drug (ipidacrine, 1 mg / kg, per os) were administered for 60 days. Further, the preservation of the memorable trace in the Morris water maze test and the acetylcholinesterase activity by photometric method in the hippocampus were evaluated. Results. In the course of the work, it was found that among the eighteen studied substances the most pronounced anticholinesterase effect provided by 3-[(E)-3-(3,5-ditret-butyl-4-hydroxy-phenyl)-3-oxo-prop-1-enyl]-6-methoxy-chromene-4-one, the use of which at a dose of 40 mg/kg (oral), reduced the activity of hippocampus acetylcholinesterase by 50.5% (p<0.05) and contributed to the preservation of spatial memory in rats equally with the reference drug. Conclusion. The study demonstrated that the use of 3-formylchromone derivatives and to a greater extent 3-[(E)-3-(3,5-ditret-butyl- 4-hydroxy-phenyl)-3-oxo-prop-1-enyl]-6-methoxy-chromene-4-one contributed to the preservation of a memorable trace in animals with experimentally modeled Alzheimer's disease, which may be associated with the anticholinesterase effect of these compounds.

Relevance. Studies of the effectiveness use of 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate (acexamate) as an ointment for the treatment of burn wounds in animals have shown the prospects of its use as a regenerant and reparant. One of the important stages of the pharmacological study medicines for external application is the assessment of resorption. These studies require the implementation of precise and reproducible bioanalytical techniques. Aim: to design and validate a chromatography-mass spectrometric technique for the quantitative determination of 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate in rat blood plasma for subsequent evaluation of the substance resorption from medicines for external application. Material and methods. The object of the study was 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate, which was quantified in rat blood plasma with HPLC method using Agilent Technologies 1260 Infinity II and AB Sciex 3200MD mass spectrometer. Chromatograms of 2-ethyl-6-methyl-3-hydroxypyridine, acexamic acid and sulfacetamide (internal standard) were constructed in the MRM mode. Chromatographic separation of analytes was carried out using a Phenomenex Synerdgi C18 column of 4 microns, 2x50 mm, elution was fulfilled in a gradient mode with a mixture of water and absolute methanol. Calibration standards, quality control samples and blank samples were analyzed. For the developed method, the analytical range, the detection limit, the lower limit of quantitative determination, linearity were determined. The method was validated by the following indicators: selectivity, matrix effect, degree of extraction, substance transfer, accuracy and precision, stability. The developed technique was used to evaluate the resorption of 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate from ointment after a single application to the surface of burn defects of the rat skin. Results. 2 hours after applying the ointment, the concentrations of 2-ethyl-6-methyl-3-hydroxypyridine and acexamic acid in the rat blood plasma were 18.05±0.96 ng/ml and 21.62±1.12 ng/ml, respectively, in terms of 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl- 6-aminohexanoate. The obtained results indicate a slight resorption of the test substance through the surface of the burn defect. Conclusion. The developed method for the quantitative determination of 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexa-noate in rat blood plasma is selective, accurate, precise, linear and meets the requirements for the validation of bioanalytical methods in all parameters.