A5091611559- Advanced Glycation End Products research
- Synthesis and biological activity
- Quinazolinone synthesis and applications
- Adenosine and Purinergic Signaling
- Retinal Diseases and Treatments
- Neurological Disorders and Treatments
- Synthesis of heterocyclic compounds
- Natural Antidiabetic Agents Studies
- Protein Kinase Regulation and GTPase Signaling
- S100 Proteins and Annexins
- Immune cells in cancer
- Pneumocystis jirovecii pneumonia detection and treatment
- Wnt/β-catenin signaling in development and cancer
- Peroxisome Proliferator-Activated Receptors
- Synthesis of Indole Derivatives
- Macrophage Migration Inhibitory Factor
- Synthesis and Biological Evaluation
- Redox biology and oxidative stress
- Circadian rhythm and melatonin
- Insect Resistance and Genetics
- Inflammasome and immune disorders
- Pharmacological Receptor Mechanisms and Effects
- Retinal Imaging and Analysis
- Estrogen and related hormone effects
- Autophagy in Disease and Therapy
Volgograd State Medical University
2018-2025
Taipei Medical University
2024
Cardinal Tien Hospital
2024
Volgograd State University
2023
Abstract Chronic inflammation is a key pathogenic driver in cardiovascular, neurodegenerative and metabolic diseases. Previously we identified highly active GSK3β inhibitors with antidiabetic potential among 3,5‐disubstituted indolin‐2‐one derivatives. We found that these derivatives also possess direct antioxidant activity, which was shown luminol‐H 2 O ABTS vitro systems IC 50 level up to 6.0 34.6 µM respectively. an essential part LPS‐induced NF‐κB NLRP3 pathways activation. Hence, the...
The enzyme NRH:quinone oxidoreductase 2 (NQO2) plays an important role in the pathogenesis of various diseases such as neurodegenerative disorders, malaria, glaucoma, COVID-19 and cancer. NQO2 expression is known to be increased some cancer cell lines. Since 3-arylidene-2-oxindoles are widely used design new anticancer drugs, kinase inhibitors, it was interesting study whether structures have additional activity towards NQO2. Herein, we report synthesis novel inhibitors. It demonstrated that...
The problem of lung damage originating from excessive inflammation and cytokine release during various types infections remains relevant stimulates the search for highly effective safe drugs. biological activity latter may be associated with regulation hyperactivation certain immune cells enzymes. Here, we propose design synthesis amino derivatives 4,6- 5,7-diaryl substituted pyrimidines [1,2,4]triazolo[1,5-a]pyrimidines as promising double-acting pharmacophores inhibiting IL-6 NO....
Acute lung injury remains a challenging clinical condition, necessitating the development of novel, safe and efficient treatments. The prevention macrophage M1-polarization is viable venue to tackle excessive inflammation. We performed phenotypic screening campaign identify azolopyrimidine compounds that effectively inhibit LPS-induced NO synthesis interleukin 6 (IL-6) secretion. identified lead compound 9g inhibits IL-6 secretion with IC50 3.72 µM without apparent cytotoxicity minimal...
The activation of microglia and the production cytokines are key factors contributing to progressive neurodegeneration. Despite well-recognized neuronal programmed cell death regulated by microglial activation, themselves is less investigated. Nucleotide-binding oligomerization domain, leucine-rich repeat-containing X1 (NLRX1) functions as a scaffolding protein involved in various central nervous system diseases. In this study, we used SM826 cells understand role NLRX1 lipopolysaccharide...
The Na+/H+ exchanger isoform 1 (NHE-1) attracts ongoing attention as a validated drug target for the management of cardiovascular and ocular diseases owing to cytoprotective, anti-ischemic anti-inflammatory properties NHE-1 inhibitors. Herein we report novel inhibitors realized via functionalization N1-alkyl quinazoline-2,4(1H,3H)-dione quinazoline-4(3H)-one with N-acylguanidine or 3-acyl(5-amino-1,2,4-triazole) side chain. Lead compounds show activity in nanomolar range. Their...
Based on the methodology of artificial neural networks, models describing dependence level RAGE inhibitory activity affinity compounds for target proteins RAGE-NF-kB signal pathway have been costructed. A validated database structures and levels 183 known compounds, which were tested was formed. The analysis AGE-RAGE signaling pathways carried out, 14 key nodes found, 34 relevant identified. 66 valid 3D 22 chain compiled. Ensemble molecular docking inhibitors into sites performed minimum...
A new series of quinoxaline derivatives,
Quinazolines are a rich source of bioactive compounds. Previously, we showed NHE-1 inhibitory, anti-inflammatory, antiplatelet, intraocular pressure lowering, and antiglycating activity for series quinazoline-2,4(1H,3H)-diones quinazoline-4(3H)-one guanidine derivatives. In the present work, novel N1,N3-bis-substituted quinazoline-2,4(1H,3H)-dione derivatives bearing two moieties were synthesized pharmacologically profiled. The most potent inhibitor 3a also possesses antiplatelet...
Aim.Glaucoma is a whole group of diseases caused by increased intraocular pressure (IOP), leading to atrophy the optic nerve and irreversible blindness. Melatonin has wide range biological activity, including antioxidant antiglaucoma, but its use limited insufficient stability duration action. To search for new, more effective antiglaucoma agents among derivatives 3-arylidene-2-oxindole, melatonin analogues, quinonoxidoreductase 2 (NQO2) inhibitors was performed, activity determined effect...
Diabetic retinopathy is the most common retinal vascular disease, affecting retina's blood vessels and causing chronic inflammation, oxidative stress, ultimately, vision loss. Diabetes-induced elevated glucose levels increase glycolysis, main pathway for methylglyoxal (MGO) formation. MGO a highly reactive dicarbonyl rapid glycation compound to form endogenous advanced end products (AGEs). can act both intra- extracellularly by glycating molecules activating RAGE pathway. This...
For 14 main nodes of the RAGE-NF-kB signaling pathway 34 types monofunctional proteins, subunits and isoforms have been identified that are related to development pathies in diabetes mellitus Alzheimer's disease. human, 583 experimental X-ray 1668 theoretical 3D models these biotargets were found, a primary verification their validity was performed. signal database 826 adequate model protein-targets Homo sapiens has formed.
Development of novel agents that prevent thrombotic events is an urgent task considering increasing incidence cardiovascular diseases and coagulopathies accompany cancer COVID-19. Enzymatic assay identified GSK3β inhibitors in a series 3-arylidene-2-oxindole derivatives. Considering the pivotal role platelet activation, most active compounds were evaluated for antiplatelet activity antithrombotic activity. It was found inhibition by 2-oxindoles correlates with activation. The inhibitor 5a...
Abstract The Na + /H exchanger isoform 1 (NHE-1) attracts ongoing attention as a validated drug target for the management of cardiovascular and ocular diseases owing to cytoprotective, anti-ischemic anti-inflammatory properties NHE-1 inhibitors. Herein we report novel inhibitors realized via functionalization N -alkyl quinazoline-2,4(1 H ,3 )-dione quinazoline-4(3 )-one with -acylguanidine or 3-acyl(5-amino-1,2,4-triazole) side chain. Lead compounds show activity in nanomolar range. Their...