2-Alkyl(aryl)-quinazolin-4(3H)-thiones, 2-R-(quinazolin-4(3H)-ylthio)carboxylic acids and amides: synthesis,molecular docking,antimicrobial and anticancer properties

In this study, a series of novel 2-alkyl(aryl)-quinazolin-4(3H)-thiones, 2-R-(quinazolin-4(3H)-ylthio)carboxylic acids and amides were synthesized and evaluated for antimicrobial and anticancer activities. Their structure was confirmed by elemental analysis and spectral data (FT-IR, LC-MS, ¹H-NMR). Antimicrobial activity was tested in vitro against Staphylococcus aureus, Enterococcus faecalis, Enterobacter aerogenes, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia, Candida albicans and NCI in vitro preliminary anticancer activity against nine different cancer types. The most active antibacterial and antifungal compounds were: 2.1, 2.2 and 2.4. The introduction of the carboxylic acid or amide residue into the fourth position of quinazolin-4(3H)-thione resulted in the absence of antimicrobial activity. Substance 3.8 inhibited renal cancer UO-31 line and 2.18 – leukemia CCRF-CEM. The results of in silico molecular docking for DHFR and CK2 kinase had no correlation with in vitro properties, proposing the presence of other biological activity pathways.     

Adaptive features of natural killer cells,lymphocytes of innate immunity

Natural killer cells (NK cells) are traditionally attributed to the innate immune system. It is considered that previously received stimuli have little effect on the functioning of these immune cells. Indeed, NK cells even without prior sensitization provide a rapid effector response against tumor, virus-infected, or otherwise damaged cells. They have a limited repertoire of receptors, the expression of which does not require somatic recombination. However, recent data indicate that NK cells may acquire the properties specific to adaptive immune cells. In particular, NK cells have been shown to possess the features of immunological memory, namely, the ability to more quickly and effectively respond to a repeated stimulus. The mechanisms of memory acquisition in NK cells differ from those implemented in T and B lymphocytes and are still rather vague. Presumably, some of these mechanisms underlie the significant phenotypic and functional NK cell diversity emerging during their differentiation. The recent data accumulated in this area considerably change the existing immunology paradigm, which postulates a clear delineation of the adaptive and innate immune cells. The published data on phenotypic and functional characteristics of NK cells and particular changes in these characteristics during NK cell differentiation and generation of memory-like NK cells are reviewed.     

The adhesion of lactic acid bacteria to the intestinal epithelium of agricultural animals

The lactic acid bacteria isolated from different ecological niches are established to be able to adhere in vitro to the intestine epithelium of pigs and cattle. The studied strains of enterococci have a higher index of adhesiveness (5.7-2.24) as compared to lactic acid bacilli (3.34-1.08). Detection of the lactic acid bacteria ability to adhere to intestine enterocytes of agricultural animals served as a premise to use those bacteria when constructing preparations of the directed action on the basis of living cultures.     

Experimental and clinical study of nitazol as an antibacterial drug in the complex treatment of peritonitis

Antibacterial properties of the Soviet drug nitazol which is a derivative of imidazole were studied. It was shown that nitazol in a dose of 4-8 micrograms/ml was highly active against gram-negative nonsporulating anaerobes, gram-positive anaerobic cocci and spore-forming Clostridia spp. Unlike metronidazole, it was efficient against both standard and clinical strains of facultative anaerobes such as E. coli, S. aureus and Klebsiella spp. isolated from patients with peritonitis and being poly-resistant to antibiotics. It was found in vitro that the antibacterial effect of nitazol was higher when it was used in combination with some antibiotics. It was demonstrated on experimental models of peritonitis caused by Staphylococcus spp. and E. coli in mice that nitazol used alone or in combination with gentamicin had a favourable effect on the animal survival and lifespan. The combination of nitazol with gentamicin was applied in the combined treatment of appendicular peritonitis in 80 children and its high therapeutic efficacy was stated. Nitazol is useful as an antibacterial drug in the combined treatment of children with purulent peritonitis.     

Age-related characteristics of the role of the endothelium in the response of vascular smooth muscles to hormones. The role of ultrastructural changes

The experiments performed on isolated preparations of femoral artery and aorta of the mature and old rats as well as on those of coronary arteries of adult and old subjects failed to reveal direct participation of endothelium in the realization of insulin and vasopressin effects on the smooth muscles of the vessels studied. However, the endothelium modulated their influence on the vessels in the mature age. The lack of modulating effect of the endothelium in old age may be a result of its structural changes and thickening of a hemato-cellular barrier of the vessel wall observed by electron microscopy.     

Effect of exogenic hypercapnia on external respiration and oxygen transport function of lungs

The functioning of the respiratory system and oxygen-transport function of the lungs were estimated in experiments on healthy people under the effect of exogenic hypercapnia. The external respiration is activated under conditions of hypercapnia of the given degree, an increase in the total and alveolar ventilation of the lungs testifies to this fact. Age differences are found in diffusive and specific diffusive capacity of the lungs for O2, which indicates to changes in the oxygen-transport function of the lungs. In teenagers the diffusive capacity of the lungs changes due to the gas-exchange surface area and in people of middle age - due to changes in the diffusive properties of the lungs air-blood barrier.