ОСОБЕННОСТИ ХЕМИЛЮМИНЕСЦЕНТНОЙ АКТИВНОСТИ ТРОМБОЦИТОВ В НОРМЕ И ПРИ ИШЕМИЧЕСКОЙ БОЛЕЗНИ СЕРДЦА

The aim of the study was to study the characteristics of the chemiluminescent activity of platelets in normal and coronary heart disease. The study involved 35 patients with coronary artery disease and 16 relatively healthy people. The object of study is peripheral blood. The result was significant differences in the intensity of luminescence of platelets. Patients have increased luminescence, and therefore increased production of reactive oxygen species. This feature of chemiluminescence is associated with a change in the functional activity of cells in CHD.Целью исследования явилось изучение особенностей хемилюминесцентной активности тромбоцитов в норме и при ишемической болезни сердца. В исследование приняли участие 35 больных ИБС и 16 относительно здоровых людей. Объект изучения – периферическая кровь. Результатом стали достоверные различия в интенсивности свечения тромбоцитов. У больных наблюдается повышенное свечение, а значит и увеличенное продукция активных форм кислорода. Данную особенность хемилюминесценции связываем с изменением функциональной активности клеток при ИБС

Silver(I) complexes with phenolic Schiff bases: Synthesis, anti-bacterial evaluation and interaction with biomolecules

Novel Ag(I) complexes (2a–2c) with phenolic Schiff bases were synthesized using 4,6-di-tert-butyl-3-(((5-mercapto-1,3,4-thiadiazol-2-yl)imino)methyl)benzene-1,2-diol (1a), 4,6-di-tert-butyl-3-(((4-mercaptophe­nyl­)­imino)­methyl)benzene-1,2-diol (1b), and 4,6-di-tert-butyl-3-(((3-mercaptophenyl)imino)methyl)­benzene-1,2-diol (1c). They were examined by elemental analysis, FT-IR, UV-Vis, 1H-NMR spectroscopy, XRD, cyclic voltammetry, conductivity measurements, and biological methods. The complexes are characterized by distorted geometry of the coordination cores AgN2S2 (2c), AgNS (2b) and AgS2 (2a). These stable complexes were not typified by the intramolecular redox reaction in organic solvents resulting in the formation of silver nanoparticles (AgNPs). Antibacterial activity of 1a–1c and 2a–2c was evaluated in comparison with AgNPs and commonly used antibiotics. All the complexes were more active than the ligands against the bacteria tested (14), but they were less active than AgNPs and commonly used antibiotics. Both 1a–1c and their complexes 2a–2c exhibited the capability for the bovine heart Fe(III)-Cyt c reduction. The ligands 1b and 1c were characterized by the highest reduction rate among the compounds under study, and they showed a higher reducing ability (determined by cyclic voltammetry) as compared with that of their Ag(I) complexes 2b and 2c

Synthesis, Characterization and Biological Activity of Hydrazones and Their Copper(II) Complexes

The fundamental importance of copper as a redox-active metal essential to the functioning of several metabolic enzymes provides a wide range of its biological activity pathways. Copper(II) coordination compounds are known to exhibit potent antiproliferative, antibacterial, nuclease, anti-inflammatory and antimycobacterial activities. Hydrazones are organic ligands commonly used for complexation with copper(II) that possess antibacterial, antiviral and antifungal properties. Copper–ligand interaction might facilitate charge delocalization and increase net hydrophobicity of the system, resulting in its enhanced pharmacological activity. Coordination compounds of Cu(II) with 4,6-di-tert-butyl-2,3-dihydroxybenzaldehyde derived hydrazone, nitrofurantoin and ftivazide have been synthesized, characterized by means of elemental and XRD analysis, FT-IR, UV-Vis and NMR spectroscopy and tested for antibacterial activity in vitro on Gram-positive and Gram-negative bacteria

Synthesis, Characterization and Biological Activity of Hydrazones and Their Copper(II) Complexes

The fundamental importance of copper as a redox-active metal essential to the functioning of several metabolic enzymes provides a wide range of its biological activity pathways. Copper(II) coordination compounds are known to exhibit potent antiproliferative, antibacterial, nuclease, anti-inflammatory and antimycobacterial activities. Hydrazones are organic ligands commonly used for complexation with copper(II) that possess antibacterial, antiviral and antifungal properties. Copper–ligand interaction might facilitate charge delocalization and increase net hydrophobicity of the system, resulting in its enhanced pharmacological activity. Coordination compounds of Cu(II) with 4,6-di-tert-butyl-2,3-dihydroxybenzaldehyde derived hydrazone, nitrofurantoin and ftivazide have been synthesized, characterized by means of elemental and XRD analysis, FT-IR, UV-Vis and NMR spectroscopy and tested for antibacterial activity in vitro on Gram-positive and Gram-negative bacteria

Alkyl Derivatives of Perylene Photosensitizing Antivirals: Towards Understanding the Influence of Lipophilicity

Amphipathic perylene derivatives are broad-spectrum antivirals against enveloped viruses that act as fusion inhibitors in a light-dependent manner. The compounds target the lipid bilayer of the viral envelope using the lipophilic perylene moiety and photogenerating singlet oxygen, thereby causing damage to unsaturated lipids. Previous studies show that variation of the polar part of the molecule is important for antiviral activity. Here, we report modification of the lipophilic part of the molecule, perylene, by the introduction of 4-, 8-, and 12-carbon alkyls into position 9(10) of the perylene residue. Using Friedel–Crafts acylation and Wolff–Kishner reduction, three 3-acetyl-9(10)-alkylperylenes were synthesized from perylene and used to prepare 9 nucleoside and 12 non-nucleoside amphipathic derivatives. These compounds were characterized as fluorophores and singlet oxygen generators, as well as tested as antivirals against herpes virus-1 (HSV-1) and vesicular stomatitis virus (VSV), both known for causing superficial skin/mucosa lesions and thus serving as suitable candidates for photodynamic therapy. The results suggest that derivatives with a short alkyl chain (butyl) have strong antiviral activity, whereas the introduction of longer alkyl substituents (n = 8 and 12) to the perylenyethynyl scaffold results in a dramatic reduction of antiviral activity. This phenomenon is likely attributable to the increased lipophilicity of the compounds and their ability to form insoluble aggregates. Moreover, molecular dynamic studies revealed that alkylated perylene derivatives are predominately located closer to the middle of the bilayer compared to non-alkylated derivatives. The predicted probability of superficial positioning correlated with antiviral activity, suggesting that singlet oxygen generation is achieved in the subsurface layer of the membrane, where the perylene group is more accessible to dissolved oxygen

Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted great interest in novel broad-spectrum antivirals, including perylene-related compounds. In the present study, we performed a structure–activity relationship analysis of a series of perylene derivatives, which comprised a large planar perylene residue, and structurally divergent polar groups connected to the perylene core by a rigid ethynyl or thiophene linker. Most of the tested compounds did not exhibit significant cytotoxicity towards multiple cell types susceptible to SARS-CoV-2 infection, and did not change the expressions of cellular stress-related genes under normal light conditions. These compounds showed nanomolar or sub-micromolar dose-dependent anti-SARS-CoV-2 activity, and also suppressed the in vitro replication of feline coronavirus (FCoV), also termed feline infectious peritonitis virus (FIPV). Perylene compounds exhibited high affinity for liposomal and cellular membranes, and efficiently intercalated into the envelopes of SARS-CoV-2 virions, thereby blocking the viral–cell fusion machinery. Furthermore, the studied compounds were demonstrated to be potent photosensitizers, generating reactive oxygen species (ROS), and their anti-SARS-CoV-2 activities were considerably enhanced after irradiation with blue light. Our results indicated that photosensitization is the major mechanism underlying the anti-SARS-CoV-2 activity of perylene derivatives, with these compounds completely losing their antiviral potency under red light. Overall, perylene-based compounds are broad-spectrum antivirals against multiple enveloped viruses, with antiviral action based on light-induced photochemical damage (ROS-mediated, likely singlet oxygen-mediated), causing impairment of viral membrane rheology