Vol 49, No 2 (2023)

Known approaches to the isolation of biopolymers, in particular nucleic acids (NAs), from biological samples are based on the binding of molecules to a sorbent (“positive selection”) with their subsequent elution using a suitable eluent. The review article discusses the physicochemical processes underlying the development of methods for isolating of NAs from biological samples. It has been shown that methods including the selective solid-phase extraction (i.e., reversible sorption) provide the possibility of miniaturization and automation of the corresponding processes. The review discusses the advantages of an alternative approach to NAs isolation based on the use of special sorbents that bind proteins and other components of biological samples, while these sorbents exhibit sorption inertness with respect to NAs (“negative selection”). Approaches providing the creation of such composite polymer-containing sorbents, which are designed for the sample preparation during molecular diagnostics, as well as the methods of their effective use are considered. It has been demonstrated that due to an interdisciplinary approach using a complex of synthetic and analytical methods, it is possible to combine as a single object of study the composite materials that are very different in structure and properties. Such nanostructured composites (based on porous silica, synthetic membranes, glass multicapillaries) contain fluoropolymers and polyanilines. The results of the use of such composites for selective isolation of NAs and/or proteins from biological samples are discussed. Alternative applications of such composites in molecular diagnostics, in particular, in mass spectrometry, are considered. Directions for expanding of the field of application of polymer-containing composites due to simultaneous use of the sorption properties of the obtained composites surface and the properties of sorbate molecules are outlined. It has been shown that both polymeric and low molecular weight modifiers of the same chemical nature are suitable for the technological preparation of such composites.

Previously undescribed esters based on N-substituted imides of cycloaliphatic carboxylic acids have been synthesized in high yields and efficient methods for their preparation have been presented. Toxicological studies of the obtained compounds were carried out using various test objects (Chlorella vulgaris, Allium cepa, Drosophila melanogaster). It was shown that the studied compounds are not active against D. melanogaster, increase the frequency of mutations in C. vulgaris and have the ability to induce chromosomal rearrangements in A. cepa. The synthesized compounds can be used in the development of antitumor drugs.

Drug delivery systems are designed to provide the necessary concentration and prolonged effect of the active substance in the body. Orally administered protein preparations require protection from proteolysis in the gastrointestinal tract. Biocompatible hydrophilic polysaccharides in the matrix are especially promising, since they do not irritate the intestines and are gradually cleaved by specific glycosidases, releasing the therapeutic agent. The introduction of an insoluble porous mineral matrix into composition of carrier makes it possible to increase the concentration of therapeutic in matrix without a significant increase in the volume of drug tablet form. In this work, a new original organic mineral carrier based on heat-treated crushed clinoptiolite zeolite in combination with natural polysaccharides from red seaweeds – agar-agar, agarose, and carrageenan was created. Granular and finely dispersed clinoptiolites in the matrix are loaded with a promising therapeutic agent, Bacillus pumilus ribonuclease (binase), which exhibits selective cytotoxicity to tumor cells. It has been established that both granular and finely dispersed zeolites in combination with polysaccharides retain protein better than pure zeolites and provide a gradual complete release of enzyme in 18 hours. At the same time, the enzyme retains its catalytic activity and induces apoptosis up to 23.8% cells of the human duodenal adenocarcinoma HuTu80. The data obtained substantiate the prospects of dosage forms based on the used organomineral carriers designing.

Based on the data of the role of Na⁺/H⁺-exchanger (NHE) in the modulation of intraocular pressure, which is the main factor in the development of glaucoma, and previously conducted studies by various authors proving the presence of inhibitory NHE-1 activity in quinazoline derivatives, nine new compounds belonging to this class were synthesized. The effect of the obtained quinazoline derivatives on the inhibition of Na⁺/H⁺-exchanger and their on intraocular pressure (IOP) in comparison with zoniporide (NHE inhibitor) and timolol (a drug for lowering IOP used in clinical practice) was studied. Among the compounds studied in vitro, all quinazoline derivatives at a concentration of 1 nM inhibited the activity of NHE-1, the most active compound was a derivative of quinazoline acetylguanidine. However, not all compounds showed IOP-reducing activity in vivo in rats. So the most active of the quinazoline derivatives are 4-oxoquinazoline acetylguanidine, its brominated derivative at position C6 and quinazoline propionylguanidine. The structure–activity analysis showed that the presence of the Br atom at the C6 position of the 4-oxoquinazoline acetylguanidine derivative leads to a maximum decrease in IOP during instillation of the solution of the compound.

Ionizable lipid ALC-0315 – ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) – is a part of the lipid matrix of the mRNA vaccine for the prevention of infection with the SARS-CoV-2 virus manufactured by Pfizer/BioNTech. This lipid provides effective assembly of the vaccine particle, protection of mRNA from premature degradation, and after endocytosis, promotes the release of nucleic acid into the cytoplasm for further processing. In this paper, a simplified and economical method for producing ALC-0315 is proposed, which can be used in the production of mRNA vaccines.