Introduction. Vitamin D deficiency is currently considered a global epidemic. Recent data highlight its pivotal role in the d of metabolic disorders, including obesity in children and adolescents.
The functionality of redox metabolism is frequently named as an important contributor to the processes of aging and anti-aging. Excessive activation of free radical reactions accompanied by the inability of the antioxidant defense (AOD) mechanisms to control the flow of the reactive oxygen species (ROS) leads to the persistence of oxidative stress, hypoxia, impaired mitochondrial energy function and reduced ATP potential. From a long-term perspective, such changes contribute to the development of chronic diseases and facilitate aging. In turn, preconditioning of a biosystem with small doses of stressful stimuli might cause mobilization of the mechanisms of AOD and control an excessive flow of ROS, which supports optimal functioning of the redox reactions. Those mechanisms are of crucial importance for anti-aging and are also known as a eustress or hormetic response. To ensure continuous support of mild pro-oxidant activity in a metabolic system, close monitoring and timely corrections preventing the development of excessive ROS production are required. The paper introduces the potential of heart rate variability (HRV) as a biomarker of functional and metabolic reserves and a tool to measure stress resilience during aging. The practical approaches to interpretation of HRV are provided based on total power, changes in total power in response to an orthostatic test and activities of all spectral components. It is suggested that the complex of those parameters can reflect the
depth of oxidative stress and may be used to guide lifestyle interventions and promote active longevity.
UDC: 615.276:547.789:542.91
Aim. Based of the Knoevenagel condensation reaction the synthesis of new rhodanine-indoline hybrid molecules for screening antibacterial and antifungal activities was accomplished. Methods. Organic synthesis, NMR spectroscopy, pharmacological screening. Results. The reaction between rhodanine-3-propanoic/ethanesulfonic acids and indolecarbaldehydes in the acetic acid provided series of 5-indolylmethylenerhodanine-3-carboxylic/sulfonic acid deriva-
tives. Based on the esterification reaction with methanol in the presence of sulfuric acid, 5-indolylmethylenerhodanine-3-propanic acid was transformed into appropriate ester for further evaluation of antimicrobial activity. The antimicrobial activity screening allowed the identification of compounds with significant effect against Escherichia coli, Staphylococcus lentus and Candida albicans with MIC/MBC/MFC values in the range of 25-50 μg/mL.
Conclusions. The synthesized 5-indolylmethylenerhodanine-3-carboxylic/sulfonic acid derivatives are a convenient platform for the development of new highly active and low-toxic agents as potential drug-like molecules with antimicrobial activity.
K e y w o r d s: synthesis, 2-thioxo-4-thiazolidinone, indolecarbaldehydes, spectral data, antimicrobial activity.
Keywords:
2-thioxo-4-thiazolidinones, indolecarbaldehydes, synthesis, cellular immunity, phagocytosis, immunotropic activity, leukocytes, guinea pigsAbstract
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
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Aim. The screening of antimicrobial and cytotoxic activities of thiazolo[4,5-b]pyridine derivatives was accomplished. Methods. The antibacterial and antifungal activities of synthesized thiazolopyridines were evaluated in vitro with the agar diffusion and broth microdilution methods using clinical and reference strains of Gram-positive, Gram-negative bacteria and yeasts. The structure-antibacterial/antifungal activity relationships of the screened compounds were established. The target compounds were screened for their cytotoxicity effects on HaCaT and HEK293 cells using MTT assay. Results. The highest antimicrobial activity was observed for compound V 2-oxo-7-thiophen-2-yl-2,3-dihydrothiazolo[4,5-b]pyridine-5-carboxylic acid with minimal inhibitory concentration (MIC) 12.5 μg/mL against Candida albicans. At the same time, the synthesized compounds were explored in the interaction with amoxicillin against multidrug resistant clinical isolates of ESβL+ Klebsiella pneumonie and Staphylococcus haemolyticus (MRSH). The best synergistic activity with amoxicillin was exhibited by compound VI. HaCaT human keratinocytes and HEK293 human embryonic kidney cells demonstrated resistance to the thiazolopyridine derivatives treatment and did not reach the IC50 value up to 100 µM. Conclusions. The tested thiazolopyridines constitute an interesting background for further development of new chemotherapeutic agents. K e y w o r d s: heterocyclic compounds, thiazolidinones, thiazolo[4,5-b]pyridines, antimicrobial activity, antiproliferative activity