УДК 613.495:615.454.1-099:615.065]-053.2-092.4/.9

Анотація. Проведено експериментальне дослідження алергенної та імунотоксичної дії шампунів та гелів для купання дітей, виробництва ТОВ “ГАЛВОКС” на мурчаках. Показано, що засоби не володіють алергенною та імунотоксичною дією, проте можуть викликати алергізацію організму дітей з індивідуальною чутливістю. Перкутанна сенсибілізація засобами викликала у піддослідних мурчаків підсилення фагоцитарної активності нейтрофілів та збільшення кількості лейкоцитів. За результатами алерготестів in vivo відмічено достовірні зміни РСЛЛ, що може свідчити про здатність засобів до індукції реакції гіперчутливості сповільненого типу.

 Abstract. An experimental study of the allergenic and immunotoxic effect of shampoos and gels for bathing children of the Ukrainian manufacturer GALVOX LLC on guinea pigs was conducted. The obtained results make it possible to classify these cosmetics as those that do not have an allergenic and immunotoxic effect, but can cause an allergic reaction of the body, taking into account individual sensitivity. Percutaneous sensitization by these means caused an increase in the phagocytic activity of neutrophils and an increase in the number of leukocytes in test ants. Also, among allergotests in vivo, reliable changes in RSLL were noted, which may indicate the ability of the drug to induce a delayed-type hypersensitivity reaction.

УДК 615.9:577.19:595.78:001.891.53

Анотація. Проведено токсикологічну оцінку інсектициду феромону Lepidoptera. Встановлено, що феромон Lepidoptera при однократному пероральному введенні, інгаляційному  впливі,  нанесенні  на  шкіру  відноситься  до  4  класу  небезпечності. Не   володіє подразнювальним ефектом при попаданні на шкіру та слизові оболонки, не викликає сенсибілізацію організму. Гранично допустима концентрація феромону Lepidoptera у повітрі робочої зони 10 мг/м³, 4 клас небезпечності, пари.

Abstract. A toxicological evaluation of the Lepidoptera pheromone insecticide was  carried out. It has been established that the pheromone of Lepidoptera belongs to the 4th class of danger upon single oral administration, inhalation exposure, application to the skin. Does not have an irritating effect upon contact with the skin and mucous membranes,  does  not  cause  sensitization  of  the  body.  The  maximum  permissible concentration of Lepidoptera pheromone in the air of the working area is 10 mg/m³, hazard class 4, vapors.

Keywords: 

2-thioxo-4-thiazolidinones, indolecarbaldehydes, synthesis, cellular immunity, phagocytosis, immunotropic activity, leukocytes, guinea pigs

Abstract

The aim. To study the cell immunity status under influence of 3-[5-(1H-indol-3-ylmethylene)-4-oxo-2-thioxo-thiazolidin-3-yl]-propionic acid, as a prominent 4-thiazolidinone derivative and a class of biologically active compounds with polypharmacological properties.

Materials and methods. Experimental method on the model of laboratory animals (guinea pigs); intradermal allergy tests; relative and absolute content in the peripheral blood of T- and B-lymphocytes subpopulations; hematological indexies: index of the ratio of lymphocytes and monocytes, index of the ratio of neutrophils and monocytes, index of the ratio of neutrophils and eosinophils, phagocytic index, phagocytic number; ELISA; organic synthesis; pharmacological screening.

Results. The effect of 3-[5-(1H-indol-3-ylmethylene)-4-oxo-2-thioxo-thiazolidin-3-yl]-propionic acid has antifungal properties and affect cellular component of immunity in vivo in the guinea pigs model. There are no changes in the skin of guinea pigs during and after chemical applications of the skin and after intradermal tests. The compound stimulate the immune cells, in particular the lymphocyte (increase in the absolute number of CD3 T-lymphocytes by 21.46 % and the absolute number of CD8 T-suppressors by 27.15 %), but with a selective inhibitory effect on certain units (decrease the relative number of NK cells CD16 by 11.57 % and B-lymphocytes CD22 by 23.08 %). There was an increase in the activity of the macrophage phagocytic system (increase in PN by 439.87 % and PI by 62.73 % at 120 minutes), which indicates the reliability of the absorbing function of phagocytes, but with a decrease in their ability to endocytosis (PCI decreased significantly by 78,72 %).

Conclusions. Synthesized 3-[5-(1H-indol-3-ylmethylene)-4-oxo-2-thioxo-thiazolidin-3-yl]-propionic acid has a selective activating effect on certain parts of cellular immunity and on phagocytic activity. Derivate influence on the phagocytic activity of neutrophils is ambiguous, and the effect of the compound directed to the cellular part of the immune system does not cause cellular immunodeficiency. The studied derivative is promising for further study of the drug-like molecule with antifungal and antitumor effects

Abstract: Searching for new types of biological activities among preliminarily identified hit compounds is a key challenge in modern medicinal chemistry. In our study, a previously studied 3-[5-(1H-indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl]-propionic acid (Les-6614) was screened for antimicrobial, antifungal, anti-allergic and antitumor activities. Moreover, cytotoxicity, molecular docking, and, the SwissAdme online target screening were accomplished. It was determined that the Les-6614 has slight antimicrobial and antitumor activity. However, the studied compound decreased IgE levels in sensitized guinea pigs by 33-86% and reduced IgA, IgM, IL-2, and TNF-α, indicating anti-inflammatory and anti-allergic activities. According to the SwissADME web tool, target predictions Les-6614 potentially has an affinity for Lysosomal protective protein, Thromboxane-A synthase, and PPARγ. The molecular docking confirmed that the studied 2-thioxo-4-thiazolidinone derivative showed good bonding with LLP and TXAS leading to stable protein-ligand complexes. Also, the Les-6614 is a potential PPARγ modulator, which is important in the pathogenesis of allergy, cancer, and cardiovascular diseases.