Synthesis and primary evaluation of the hepatoprotective properties of novel pyrimidine derivatives

Vyshtakalyuk, A. B.; Семенов, В. Э.; Зобов, В. В.; Galyametdinova, I. V.; Gumarova, L. F.; Парфенов, А. А.; Назаров, Н. Г.; Lenina, Oksana A.; Kondrashova, Svetlana A.; Latypov, Shamil K.; Черепнев, Г. В.; Shashyn, M. S.; Reznic, V.S.

doi:10.1134/s106816201704015x

Cited by 16 publications

(20 citation statements)

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“…On the contrary compounds (2,(4)(5)(6) promoted platelet aggregation at the concentrations as follows: (2 (1) and compound (7) had the effect at 10-5 M and 10-9-10-6 M, respectively. Thus, our experiments showed that betulin and its C-3,C-28-diphosphonium derivatives demonstrated a inhibitory activity on induced aggregation of platelets.…”

Section: P063-t | Ultrastructural Changes In Plateletsmentioning

confidence: 97%

“…from the spleen of pro-angiogenic neutrophils through the activation of sympathetic nerves C. Seignez; M. Phillipson Department of Medical Cell Biology, Biomedical Center, Uppsala University, Uppsala, Sweden Background: We recently described that hypoxic tissues induce the recruitment of a distinct population of neutrophils (CD49d + VEGFR1 high CXCR4 high and MMP9 high), called pro-angiogenic neutrophils, crucial for restoring the oxygen supply of the tissue by inducing the development of new and functional blood vessels 1,2 . This study aims to characterise the origin of the pro-angiogenic neutrophils and the signals driving their recruitment into the hypoxic tissue.…”

Section: P022-t | Tissue Hypoxia Induces the Mobilisationmentioning

confidence: 99%

“…In our previous investigations was shown that pyrimidine derivative, Russian drug Xymedon (I) have hepatoprotective properties [1]. We synthesized derivatives of Xymedon with biogenic molecules to improvement of hepatoprotective properties [2,3]. The derivative of Xymedon with L-ascorbic acid (II) leads to the most pronounced decrease of areas of liver injury [3,4].…”

Section: P080-f | Eradication Ofmentioning

confidence: 99%

“…The lining of the ducts was either pseudo-layered with hyperplastic proliferating cholangiocytes hypersecreting acidic mucopolysaccharides or atrophic. In our previous work [1] the hepatoprotective properties of the drug Xymedon and its derivatives [2] was shown. Moreover, the ability of pyrimidine derivatives to stimulating the regeneration of the spinal marrow [3] as well as the blastema of planarian [4,5] have been determined.…”

Section: P080-f | Eradication Ofmentioning

confidence: 99%

“…For each question there were 11 possible answers ranging from 0 (more conformist, relaxed or autonomous) to 10 (more competitive, tense or dependent). Each personality trait was categorized into three groups: low level (1)(2)(3)(4), moderate level (5)(6) and high level (7-10). ANOVA and Chi square tests were used to assess the association between personality traits and lifestyles, and Benjamini-Hochberg's q-value procedure for controlling false discoveries.…”

Section: Introductionmentioning

confidence: 99%

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Poster Abstract

2018

Eur J Clin Investigation

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Background: ARHGAP25, a GTP-ase activating protein for Rac is mainly expressed in hematopoietic cells and plays predominant role in regulation of neutrophilic effector functions (phagocytosis, superoxide production), as well as neutrophil recruitment and extravasation due to its effect on Rac-dependent cytoskeletal changes. These findings strongly suggest, that ARHGAP25 may be involved in regulation of inflammatory diseases as well. This led us to investigate its role in autoantibody-induced model of rheumatoid arthritis, in transgenic mice. Material and methods: After intraperitoneal injection of K/B9N mouse strain-derived serum into Arhgap25À/À (KO) and wild type (WT) mice, ankle thickness was measured and a clinical score, indicating the severity of inflammation was determined. The loss of function was investigated by hanging on the mice on a wire-grid. Neutrophil infiltration into the ankle joints and the amount of filamentary actin in infiltrated neutrophils were measured with flow cytometry, using KO Background: Alzheimer's disease, the most common form of dementia in the elderly, is characterized by a triad of pathological features: extracellular amyloid deposits predominantly composed of amyloid-b peptides, intracellular neurofibrillary tangles made of hyper-and abnormally phosphorylated Tau protein, and gliosis. Recent studies have underlined the effect of systemic inflammation on the pathophysiology of Alzheimer's disease. Neutrophils are key components of early innate immunity and contribute to uncontrolled systemic inflammation if not tightly regulated. The aim of our study was to fully characterize human circulating neutrophils at different disease stages in Alzheimer's disease. Material and methods:We analyzed neutrophil phenotypes and functions in forty-two patients with Alzheimer's disease (sixteen with mild cognitive impairment and twenty-six with dementia), and compared them with twenty-two age-matched healthy subjects. This study was performed directly in whole blood to avoid issues with data interpretation related to cell isolation procedures.Results: Blood samples from Alzheimer's diseases patients with dementia revealed neutrophil hyperactivation associated with increased reactive oxygen species production and increased levels of intravascular neutrophil extravascular traps. The homeostasis of circulating neutrophils in these patients also changed: the ratio between the harmful hyperreactive CXCR4 high/CD62L low senescent and the CD16 bright/CD62L dim immunosuppressive neutrophil subsets rose in the later stage of the disease. Interestingly, these abnormalities were greater in fast-decliner than in slowdecliner patients. Natural pseurotins are secondary metabolites of filamentous fungi possessing antimicrobial and antiparasitic activity. Interestingly a few studies suggested effects of pseurotins in eukaryotes e.g. antiangiogenic activity in chick chorioallantoic membrane assay or inhibition of IgE production by activated B-lymphocytes. In this study, we focused on effects of natural pseu...

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Section: P063-t | Ultrastructural Changes In Plateletsmentioning

confidence: 97%

Section: P022-t | Tissue Hypoxia Induces the Mobilisationmentioning

confidence: 99%

Section: P080-f | Eradication Ofmentioning

confidence: 99%

Section: P080-f | Eradication Ofmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Poster Abstract

2018

Eur J Clin Investigation

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Conjugate of pyrimidine derivative, the drug xymedon with succinic acid protects liver cells

Vyshtakalyuk

Парфенов

Gumarova

et al. 2020

J Biochem & Molecular Tox

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The aim of the study was to investigate the hepatoprotective properties of the conjugate of the xymedon drug substance with succinic acid (1a). The study presents an in vitro comparative evaluation of the cytotoxicity and cytoprotective properties of 1a and succinic acid on a cell line of normal human hepatocytes Chang Liver, and in vivo investigation of the ability of 1a to restore liver from the toxic damage caused by CCl4 in Wistar rats. It was shown that the cytotoxicity of 1a was 19.9 ± 0.8 mmol/L, and that of succinic acid was 14.1 ± 0.2 mmol/L. Against the background of d‐galactosamine exposure, the cytoprotective effect of 1a was found to be superior to that of succinic acid. It was shown that 1a caused a significant reduction in necrotic and steatosis changes in the liver and restoration of biochemical markers of cytolysis, as well as bilirubin metabolism and synthetic liver function.

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