№ 4 (2020)

Poisoning with organophosphorus compounds occupy one of the leading places in exotoxicosis. At the first stage, the detoxification of organophosphates can be provided with the help of DNA or RNA aptamers that bind the poison in the bloodstream. Currently, the main method of searching for aptamers is the experimental method of systematic evolution of ligands by exponential enrichment (SELEX). In the process of aptamer selection, the target molecule must be immobilized via the streptavidin-biotin complex. Since the poison molecule is small in size, to increase its availability for binding to aptamer, it is necessary to use a spacer between organophosphorus compounds and biotin. The aim of this work was to optimize the selection of aptamers for organophosphorus compounds by increasing the availability of a poison molecule immobilized via the streptavidin-biotin complex on the example of paraoxon. For this purpose, three spacers between organophosphorus compounds and biotin were tested using molecular modeling methods: three links of polyethylene glycol (3-PEG), four links of polyethylene glycol (4-PEG) and aminohexyl. The conformation of the biotinylated paraoxon complex with streptavidin and the interaction of paraoxon with the binding fragment of the aptamer were modeled using molecular docking and molecular dynamics methods. The ability of biotinylated paraoxon to bind to the aptamer has been evaluated by analyzing the surface area of the paraoxon available to the solvent, as well as by calculating the free binding energies. It has been shown that only in the case of aminohexyl immobilized paraoxon can contact the aptamer. At the final stage, the synthesis of paraoxon bound to biotin via aminohexyl was carried out.

Data on the biological activity of kappa-opioid receptor agonists - derivatives of three groups of compounds: 1,2-cyclohexylamine, 1,2,3,4-piperidine, 1,2,4-piperazine are presented. On the examples of 1,2-cyclohexylamine and 1,2,4-piperazine derivatives, it has been shown that a decrease in the length of the carbon chain in the phenylalkyl substituent at the nitrogen atom is accompanied by a decrease in the analgesic activity and toxicity of compounds. The replacement of chlorine atoms in the 3 and 4 positions of the phenyl ring with fluorine atoms, which are more electronegative, leads to an increase in the analgesic effect and a decrease in the toxicity of the compounds.

The article presents the results of a study of the neurotoxicological profile of the new compound AB-19, acting on collagen glycation end products (AGE) and their receptors (RAGE), for the prevention and treatment of diabetes complications. The multi-test method «S. Irwin» was used. The test results were evaluated in parallel groups receiving the substance in doses starting with the average effective dose (ED50) and with a multiple increase by 5, 10, 20 and 50 times. It was found that the compound AB-19 in doses of 20, 100 and 200 mg / kg does not affect the functional and behavioral status of animals. However, with an increase to 400 mg / kg, typical manifestations of intoxication were observed: a decrease in muscle tone, hypothermia, sedation, tachypnea. As a result of the study, it was revealed that the neurotoxicological properties of the compound AB-19 are characterized by dose-dependent activity. A minimum toxic dose of 400 mg / kg ≤ Td_min ≤ 1000 mg / kg was also indicated.

The paper considers the influence of polychlorinated dibenzo-p-dioxins, dibenzofurans, biphenyls and benz[a] pyrene on the germination of barley seeds, as well as the influence of pollutants on seed storage. As a result of the experiments, the negative effect of polychlorinated biphenyls on seed germination at a concentration of 100 μg/ kg has been found, which can be explained by the high accumulation of low-chlorinated pollutants by seeds. The negative effect of benz[a]pyrene on seed germination at concentrations of 20 and 100 μg/kg has been registered.

Assessment of the acute toxicity, safety and biological activity of lipophilic extracts of the White Sea brown algae“– S. latissima and F. vesiculosus– on the model of zoohydrobionts Daphnia magna Straus has been performed.

Two methods of obtaining dry lipid concentrate of kelp and fucus were tested. It has been shown that the acute toxicity of the lipid extract of kelp does not depend on the method of its preparation and is about 200 mg/L. The acute toxicity of fucus extract depends on the method of preparation. It is about 100 mg/L in the «cold» method of extraction and increases by an order of magnitude in the «hot» method. To study the biological activity, samples of brown algae obtained by «cold» extraction were used.

In chronic experiments, preparations of brown algae were used in a concentration of 8.0 mg/L, which was less than 0,1 LC50 of the acute toxicity of fucus and did not cause toxic effects.

For 24 days, the preparations were introduced in contact with Daphnia twice a week. Subsequently, the control and experimental hydrobionts were kept under the same conditions until the death of the last individuals. It has been shown that the preparations of S. latissima and F. vesiculosus in the proposed concentration by 20-30% increased the lifespan of Daphnia in normal conditions and by 50-60% in extreme conditions, while stimulating the reproductive activity of aquatic organisms by 3-4 times. The results obtained suggest that the studied drugs have pronounced adaptogenic and cytoprotective effects.

Sodium lauryl sulfate is the most common surfactant used in the production of detergents, chloroprene rubber, plastics, artificial furs and in pharmaceutical industry. Sodium lauryl sulfate is a moderately hazardous substance when introduced into the stomach (DL50 for white mice and rats is in the range of 2086-2700 mg/kg), has a pronounced local irritant effect on the skin and mucous membranes of the eyes, has a skin-resorptive, sensitizing and pronounced cumulative effects. The threshold for acute inhalation action is set at 15,3 mg/m3 for changes in the function of the nervous system and irritating effects on the mucous membranes of the upper respiratory tract (an increase in the total number of cells in the nasal flushes).

Recommended for approval tentative safe exposure level of sodium lauryl sulfate in the air of the working area is 0.2+ mg/m3 (aerosol).