Biophysical Bulletin

Background: During the past decades, increasing attention has been given to elucidating the molecular details of interactions between the pharmacological agents and nucleic acids since the drug–DNA complexation may lead to impairment of DNA replication, strand breaking and mutations. A variety of techniques have been developed to characterize the drug-nucleic acid binding, among which the fluorescence dye displacement assay is one of the most informative approaches. Recently, it was demonstrated that cyanine dyes can be successfully employed for the high throughput screening of the interactions between nucleic acids and drugs. To the best of our knowledge, so far, the potential application of cyanine dyes for the drug-displacement studies remains insufficiently evaluated. Objectives: The aim of the present study was to investigate the ability of a novel cyanine dye to serve as a competitor for the potential antitumor compounds, lanthanide complexes bearing europium (III) tris-β-diketonate (EC) for the DNA and RNA binding sites. Materials and methods: Calf thymus DNA, yeast RNA, trimethine cyanine dye and lanthanide complexes bearing europium (III) tris-β-diketonate were used for sample preparation. The fluorescence data were acquired using Perkin-Elmer LS-55 spectrofluorimeter. Results: Using the fluorescence spectroscopy technique we conducted the displacement reaction trimethine cyanine dye/europium coordination complexes in the presence of double stranded DNA and single-stranded RNA. An increase of the EC concentration in the systems AK3-5/DNA or AK3-5/RNA was followed by a gradual reduction in the AK3-5 fluorescence intensity, indicating that europium (III) tris-β-diketonate compounds can serve as competitors for the trimethine cyanine dye on the nucleic acids. Both the drug chemical structure and the type of nucleic acid proved to control the extent of EC-induced decrease of AK3-5 fluorescence in the presence of the DNA or RNA. Conclusion: By recruiting the potential antitumor agents europium chelate complexes as the competitive ligands for the cyanine dye for the DNA and RNA binding sites, we found that a novel trimethine compound can be effectively used in the fluorescence drug displacement assays.

О Zhytniakivska

U Tarabara

A Kurutos

A Zabrudska

K Vus

V Trusova

G Gorbenko

T Deligeorgiev

Olga Zhytniakivska

Novel cyanine dye as competitive ligand for probing the drug–nucleic acid interactions

新型菁染料作为竞争配体用于探测药物-核酸相互作用

Background: While antibiotic cycloserine (CYS) is widely applied in the treatment of tuberculosis, our knowledge of the drug intermolecular interactions with targeting biomolecules and other drugs remains incomplete. It is believed that the CYS antibacterial activity is related to inhibiting the bacterial cell wall biosynthesis. On the other hand, intermolecular interactions of CYS with ascorbic acid (ASC) molecules is worth of studying taking into account that ASC can be used as supporting vitamin preparation or can be affiliated with the patients nutrition. Objectives: The purpose of the current model study are to examine biologically significant intermolecular interactions of CYS with N-acetyl-D-glucosamine (NAG) as one of the main component of peptidoglycan of bacterial cell wall and to verify the possibility of noncovalent complexes formation between CYS and ASC molecules using electrospray ionization mass spectrometry (ESI MS) technique. Materials and methods: The objects of the study are model systems composed of CYS and NAG or CYS and ASC prepared in a polar methanol solvent for the ESI MS probing. ESI mass spectra are obtained using the approach earlier developed by us for investigation of the noncovalent complexation of drugs with targeting biomolecules. Results: The experiments reveal that the ESI mass spectrum of (CYS–NAG) model system contains peaks of protonated molecular clusters of CYS with NAG: [CYS•NAG•H]+ and [CYS•2NAG•H]+. Existing of such peaks in the spectrum testifies to formation of stable noncovalent complexes between CYS and NAG in the studied solution. ESI MS examining of (CYS–ASC) system reveals the noncovalent pair complexation of CYS and ASC molecules confirmed by the recording of intensive peak of [CYS•ASC•H]+ cluster in the spectrum. Conclusions: The ESI MS findings point to the possibility of noncovalent complexation of CYS with NAG in the polar media including biological systems. Such complexation between the antibiotic and NAG as component of peptidoglycan of bacterial cell wall is considered to be biologically significant for the process of the cell wall biosynthesis inhibiting by CYS. Stable noncovalent complexes formation between the CYS and ASC molecules is suggested as a potential molecular mechanism of the drugs activity modulation under their joint usage.

V Pashynska

M Kosevich

A Gomory

B Verkin

Т Аскорбіновою

Кислотою Пашинська

М Косевич

А Гоморі

Mass spectrometry study of noncovalent complexes formation of antibiotic cycloserine with N-acetyl-D-glucosamine and ascorbic acid

抗生素环丝氨酸与N-乙酰-D-氨基葡萄糖和抗坏血酸非共价复合物的质谱研究

Background: Mechanical properties of light are widely used in applied areas, such as optical trapping and manipulation, sorting, deformation of biological cells and molecules. In general, the evanescent field may exhibit three components of optical momentum and spin angular momentum (spin), which manifest themselves in the occurrence of corresponding components of optical force and torque. Such extraordinary properties of evanescent waves open up new possibilities for manipulating of micro- and nanoobjects, in comparing with classical optical tweezers and manipulators, which can be used for solving the applied problems, in particular, of biomedicine. Objectives: Aim of this work is to analyze and summarize recent studies regarding to the mechanical influence of evanescent field on micro- and nanoobjects, in particular, related to the influence of transverse components of optical momentum and spin. Materials and methods: Method of momenta allows one to distinguish in an evanescent field the action of optical forces and torques, associated with the components of optical momentum and angular momentum of different nature and action direction, depending on the polarization of the incident wave. Experimental methods of particle manipulation in the near field allow visualizing such an influence, which makes it possible for solving the applied problems. Results: Recent studies demonstrate the action on nano- and microobjects of such "extraordinary" optical momentum and spin components, as transverse spin momentum, transverse spin, transverse imaginary optical momentum component, and vertical spin. Using, in particular, the latter, to solve the applied problems of biomedicine is proposed, such as transporting of therapeutic agents to pathological areas or restoring vascular patency and tissue blood supply. Conclusions: Obtained results of theoretical and experimental investigation of the mechanical action of the optical momentum and spin components of evanescent field allow us to extend the approaches of optical manipulation of micro- and nanoobjects, with the possibility of applications, in particular, for the problems of biomedicine.

O Angelsky

Influence of components of optical momentum and spin of evanescent waves on micro- and nanoobjects (Review)

消逝波的光动量和自旋分量对微纳物体的影响（综述）

Background: Considered merocyanine molecules have donor D and acceptor A moieties connected by polymer chain. The conjugated donor D and acceptor A parts of merocyanine molecules are planar in the ground state. The D-π-A molecular complexes can change their conformations in an excited state due to cis-trans-conformational transitions. The viscosity of the solvent affects conformational changes, photoluminescence (PL) decay and PL lifetime. Therefore the PL of merocyanine molecules strongly depends on medium in excited and ground states. A nematic liquid crystal was utilized as a solvent for merocyanine molecules since it is characterized by long range order, orientates merocyanine molecules along its axis and is sensitive to external electro-magnetic field. The molecules with conjugated donor D and acceptor A parts are promising for molecular electronics (instruments for recording and processing information), optoelectronics (laser technologies) and biological research (fluorescent probes like prominent thioflavin T), since their PL essentially depends on the nature of the environment. Objectives: The main objective of this paper is to investigate and explain impact of liquid crystal medium on considered molecules. Also influence of molecular conformational changes on their spectral properties is considered. Materials and Methods: Two types of merocyanine molecules M-1 and M-2 were investigated. The spectral properties of molecules in different organic solvents such as acetonitrile, toluene, glycerol, and in 4-pentyl-4′-cyanobiphenyl (5CB) liquid crystal were compared. Stationary and time-resolved emission spectra of molecular merocyanine solutions were used to investigate conformational changes of molecules. To determine a lifetime of molecular excited states, a technique of Time Correlated Single Photon Counting with picosecond resolution in time was used. Results: The results indicate that optical properties strongly depend on conformation of conjugated donor-π-acceptor compounds. A relaxation of dye molecules to the ground state is accompanied by conformational changes. The quantum yield and lifetime of PL increase in more viscous solvents. The liquid crystal made conformational changes of considered molecules in ground and excited states. Conclusions: Analysis of the results serves as a basis for constructing a theory that explains properties of D-π-A molecular compounds under optical excitation. The molecular pairs are formed by merocyanine and liquid crystal molecules. The liquid crystal molecule defines conformation of merocyanine molecule in a pair. Moreover, both types of merocyanine molecules in liquid crystal have the same conformation. This hypothesis explains similarities of optical properties of M-1 and M-2 molecules in liquid crystal.

M. B. Malynovskyi

M. M. Sevryukova

Yu. P. Piryatinski

Fluorescence of molecular composites that consist of nematic liquid crystal and merocyanins

液晶与部花菁分子复合物的荧光特性

Background: The technological developments for nanocellulose production from cheaper plant materials compared to wood, in particular, agricultural waste is an urgent task of nanobiophysics. The discovery of possibility of expanding the functional characteristics of materials in compositions with modified cellulose particles essentially stimulated the interest of researchers in cellulose composites. Surface modification of cellulose particles by functional materials, such as dyes, metal oxides, silicon, allows applying composites with modified cellulose in various areas of modern industry. A significant improvement in the operational performances of functionalized cellulose particles can be achieved by using them as filler in polymers. Epoxy resin compositions with modified and unmodified cellulose particles, studied in present work, are an example of hybrid biosystem. The interfacial interaction of filler particles with the epoxy matrix, their concentration and dispersion can change the physical and chemical properties of the biopolymer and the functional parameters of biocomposites. Studying the influence of external fields on the physical and chemical properties of epoxy resin-based biosystems and their influence on operational parameters seems to be an urgent problem of advanced and sustained materials science. Objectives: The purpose of this work was to develop an effective nanocellulose synthesis from plant materials and surface functionalization of micro- and nanocellulose particles with clathrochelate iron (ΙΙ) dye as well obtaining biocompositions of epoxy resin with functionalized and non-functionalized micro- and nanocellulose, and to explore of the morphology, chemical resistance, mechanical and thermal properties of epoxy composites with cellulose micro and nanoparticles. Materials and methods: The studying objects were the composites of epoxy resin Eposir-7120 with a polyethylene polyamine “PEPA” hardener in a ratio of 6.2:1 and 10% cellulose micro and nanoparticles. The microcellulose obtained from wood has been a commercial product. Nanocellulose has been synthesized from organosolv cellulose obtained from Miscanthus x giganteus stalks. Surface modification of micro- and nanocellulose was performed using the clathrochelate iron (ΙΙ) dye. The specific surface area of cellulose particles was determined using low-temperature nitrogen adsorption-desorption according to the Brunauer-Emmett-Teller method. Mechanical parameters were determined using universal Shopper and UMM-10 machines. Thermal analysis was performed using Q1500 analyzer. Swelling was determined by the gravimetric method. Results: Elastic modulus E, compressive strength σ and thermogravimetric parameters were determined. It was shown that in composites with micro and nanocellulose the E rises in 7.0–12.2% while the σ increases in 9.1% for composites with cellulose micro particles. The loading resin with nanocellulose and modified cellulose microparticles no affects the σ value of composites. The thermal stability of epoxy polymer (310°C) reduces after loading with micro and nanocellulose to 290 and 300°C, respectively. Chemical resistance of composites with both celluloses to 20% nitric acid reduces. In neutral medium swelling characterizes by rapid sorption to saturation of 15–20% acetone in 36 hours. Conclusions: Thus, the synthesis method of nanocellulose from plant materials and functionalization of its surface with clathrochelate iron (ΙΙ) were developed. Light response of dye was detected in visible spectral range. Epoxy resin composites with 10% micro and nanocellulose were obtained. The filling effect with micro- and nanocellulose at elastic modulus, compressive strength, and thermal stability of epoxycomposites was studied. The swelling processes run similarly in composites with cellulose micro and nanoparticles.

Sigar Gorel

Influence of cellulose particles on chemical resistance, mechanical and thermal properties of epoxy composites

纤维素颗粒对环氧树脂复合材料化学抗性、力学和热性能的影响

Background: An urgent problem of modern biomedicine is the search for potential ways to reduce the spread of coronavirus infections in human and animal populations and eliminate the impact of coronavirus on their bodies. Aim of the work was to determine the structural organization of C60 fullerenes in a model cell medium, to assess their potential ability to penetrate the model lipid envelope of a coronavirus, thus destroying its integrity, as well as the effectiveness of the anticoronavirus action in the in ovo system. Methods: The research was conducted using the Gromacs 2020 software package and the Charmm36 force field. The CHARMM-GUI web resource was used to construct the lipid envelope of a coronavirus. Virological and toxicological methods were used in the in ovo experiments. Results: It is shown that at the initial stages of molecular dynamics C60 fullerene forms small nanoclusters in the amount of 7–16 molecules, which is affected by the initial concentration of C60 fullerene in a model cell medium. At the same time, the shape of nanostructures for the number of molecules over 16 may differ from the correct spherical shape. It was established that C60 fullerene and its nanoclusters are able to penetrate inside the lipid envelope of a coronavirus. In particular, a single C60 molecule can migrate, completely embed itself in the lipid envelope, or move within it. It was found that C60 fullerene aqueous solution, at the maximum permissible concentration (MPC) of 30 μg/embryo, reduces the infectious activity of the chicken infectious bronchitis (CIB) coronavirus when it is used 1, 2 and 4 h after the infection of a sensitive biological system with a coronavirus. Conclusions: It is shown that aggregation of C60 fullerene in a model cell medium can occur in different ways: either before penetration into the lipid envelope of a coronavirus, or inside it. C60 fullerenes, both individually and as part of nanoclusters, are able to form pores in the envelope of a coronavirus, destroying its integrity, which possibly leads to disruption of the corresponding stages of its replication cycle and attachment to cell receptors. It was established that C60 fullerene aqueous solution, when used in the MPC value, shows antiviral activity against the CIB coronavirus in its early stages of interaction with the cell (1–4 h).

Vasyl Hurmach

Vyacheslav Karaushu

Zinaida Klestova

Volodymyr Berest

Yurii Prylutskyy

C60 fullerene nanoparticles permeability through the model lipid envelope of coronavirus and their anticoronavirus effect in the in ovo system

C60富勒烯纳米颗粒通过冠状病毒模型脂质包膜的渗透性及其在体内系统中的抗冠状病毒效应

Background: Bronchodilators, which are compounds that can relax airway smooth muscle, are perhaps the most important component of combination therapy for chronic obstructive pulmonary disease, one of the most common non-communicable diseases in the world, which is the second most lethal disease after cardiovascular disease. Unfortunately, current clinical bronchodilators, whose activity is mediated by their interaction with muscarinic acetylcholine receptors, have side effects (up to myocardial infarction) due to their cross-affinity for different types of these receptors, including those prevalent in the heart muscle. Objectives: The aim of this work is to search/develop compounds — effective bronchodilators capable of selectively inhibiting type 3 muscarinic acetylcholine receptors (M3 receptors), predominantly present in smooth muscles and not characteristic of cardiomyocytes. Materials and Methods: High-throughput virtual screening of a collection of 150,000 compounds was conducted on the spatial structure of the M3 receptor, reconstructed in our previous studies. The effect of substances on contractile activity was investigated using tensometry in isometric mode on multicellular tracheal preparations. Antagonistic activity and type of inhibition were determined against the background of acetylcholine application (concentration range 10-10–10-3 M). To establish the affinity value of the compound-antagonist, the Schild regression equation was used. Results: Based on virtual screening data, a series of compounds — amides of 1-oxo-3-phenyl-iso-chroman-6-carboxylic acid — were selected for biological testing. For two of these compounds (Compounds 1 and 7), the ability to selectively inhibit M3 receptors was demonstrated. Specifically, the affinity value pKB for Compound 1 was 7.28 ± 0.70, with an IC50 of 5.25·10-8 M. A critically important advantage of this compound is its ability, at equal concentrations, to more effectively inhibit signal transmission through M3 receptors compared to ipratropium bromide — a clinical cholinergic receptor inhibitor. Conclusions: The sufficient effectiveness of inhibition and significantly increased selectivity of the studied compounds specifically towards M3 receptors provide strong grounds to consider these compounds as promising precursors of new generation cholinolytic drugs with targeted action on M3-type cholinergic receptors.

Alex Nyporko

Olga Tsymbalyuk

Ivan Voiteshenko

Sergiy Starosyla

Mykola Protopopov

Volodymyr Bdzhola

New promising agents against COPD and asthma among the amides of 1-oxo-3-phenyl-isochroman-6-carboxylic acid

1-氧代-3-苯基异色满-6-羧酸酰胺类化合物中针对慢性阻塞性肺病和哮喘的新型有前景的药物

Background: Intercomponent drug interactions could play important role for drug release, membrane permeability and membranotropic action. Therefore, newly developed drugs need for checking their biopharmaceutical characteristics. A new analgetic drug based on paracetamol (Actimask® Acetaminoprofen) and a hepatoprotector N-acetyl-D-glucosamine has been developed, with increased safety and potentiation of the analgesic effect (Ruban O., 2022). Multibilayer lipid membranes were chosen as promising testing medium due to their proved appropriation and sensitivity for study multi-compound drug-membrane interactions. It is the basis for a kinetic approach allowing elucidation of biopharmaceutical interactions in model membrane medium. Objectives: Revealing changes of paracetamol release and membrane penetration in the new paracetamol-glucosamine analgetic drug as well as estimation the rationale of the approach developed to trace biopharmaceutical interactions in model membrane medium. Materials and Methods: L-a-dimyristoyl phosphatidylcholine (DMPC) multibilayer membrane was used as a model biomimetic testing medium. Differential scanning calorimetry (DSC) was applicated to trace kinetics of drug-membrane interactions. Results: Gelatin as a part of Actimask® increased the characteristic time of paracetamol diffusion about threefold, but it had no pronounced effect on the equilibrium paracetamol penetration into the membrane. Sole glucosamine manifested no membranotropic effect under the experimental conditions, however, in combination with gelatin, it sufficiently reduced equilibrium paracetamol penetration while paracetamol diffusion remained within the experimental error. The full drug formulation increased membrantoropic effect by 34 % in compared with sole paracetamol. Conclusions: Glucosamine and gelatin can affect both kinetic and equilibrium parameters of paracetamol-membrane interactions, while the full set of the drug components is able to increase the effect which correlates well with the previously established enhancement of analgetic effect of the drugs. The approach developed allows accurate tracing of drug release and membrane penetration depending on a set of drug components. Generally, the results obtained prove the rationale of applying the approach to pre-clinical drug examination.

O. V. Vashchenko

O. A. Ruban

I. V. Zupanets

P. V. Vashchenko

O. I. Ivaniuk

Kinetic biopharmaceutical studies of a new paracetamol–glucosamine analgetic drug

新型对乙酰氨基酚-氨基葡萄糖镇痛药物的生物药剂学动力学研究

Background: The article describes a method for calculating the permittivity of organic molecules in quantum mechanics using the well-studied Rhodamine 6G molecule as an example. The study of optical properties of large organic molecules requires not only experimental data but also the use of calculations obtained both analytically and numerically. Objectives: Methods for calculating permittivity as phenomenological characteristics of a sample are to be tested on well-studied molecules to be further applied to more complex nonlinear structures. However, the integral changes need to be approximated in the wave functions of large molecules. Material and methods: The numerical simulations in MATLAB were carried out to be compared with the data from Gaussian 09, which are accurate for such small molecules as Rhodamine 6G. MATLAB calculated permittivity values for the frequency domains corresponding to absorption and fluorescence based on the Fermi golden rule. Hence, any molecule can be represented as a composite quantum mechanical system. Meanwhile, Gaussian 09 used the DFT method to determine permittivity. Results: The Fermi golden rule can be applied due to the representation of the molecule as a complex quantum mechanical system. The proposed numerical methods minimize error by using the Dirac delta function. According to our hypothesis, the sum of the wave function of a particle in a potential well and a particle in a ring equals the wave function of the entire system, thus making it possible to study large molecules. As a result of the calculation for two wavelengths of 337 and 573 nm, the permittivity results calculated using the proposed method in MATLAB are 2.98 and 6.27, respectively. Gaussian 09 calculated the same parameters at 2.85 and 6.23. Conclusion: The resulting datasets show a high degree of correlation. Therefore, the research hypothesis has been confirmed. The selected method also proved efficient, hence the enhancement of luminescence can be achieved by changing the relaxation time of the excited state. Plasmonic nanostructures with predetermined properties will controllably enhance the resulting field by the square of the superposition modulus of their near-field. Consequently, conditions for highly coherent radiation with high intensity and polarization can be predicted and calculated before an experiment is carried out.

Iuliia Riabenko

Sergey Shulga

Konstantin Beloshenko

Calculation of the relative permittivity of Rhodamine 6G using the quantum mechanical method

量子力学方法计算罗丹明6G的相对介电常数

Background: Natural antimicrobial peptides are used in the fight against pathogens resistant to existing synthetic antibiotics. The non-specific mechanism of cytostatic action of antimicrobial peptides, in particular gramicidin S, against bacteria is also effective for damaging the cells of neoplasms. The existence of such a property in a registered antibiotic will indicate its antineoplastic potential and can be used to expand the spectrum of its therapeutic application. Aim of work is to clarify the possible antitumor effect of the antimicrobial peptide gramicidin S. Materials and Methods: Using the methods of confocal laser microscopy and light microscopy, the morphological and functional features of connective tissue cells under the influence of gramicidin S in the concentration range 0.5–50 μg/ml were studied using L929 fibroblasts cell culture. The cell area, nucleus area, and nucleus-to-cytoplasm ratio were determined. To study the migratory and proliferative activity of cells in vitro, the “scratch assay” was used, the confluency of the monolayer of cells was evaluated, morphometric studies were performed, and the relative area of the scratch was measured after 24, 48, and 72 hours. Results: The lytic effect of gramicidin S in a concentration of 50 μg/ml on L929 cells was established, in concentrations of 0.5 μg/ml and 5.0 μg/ml, the antibiotic increases the synthetic activity of cells and stimulates the proliferation of fibroblasts in a monolayer. Cell anisomorphism is more pronounced in the presence of 5.0 μg/ml gramicidin S added to the culturing medium during monolayer formation, while a one-third of the cells in the sample form a population that is morphologically different from other cells in the culture. The addition of gramicidin S at non-lytic concentrations of 0.5 and 5.0 μg/ml to unattached fibroblasts reliably inhibits monolayer formation. Under the influence of 5.0 μg/ml gramicidin S, the rate of monolayer formation is low, even despite the significant content of cells with a high nuclear-cytoplasmic ratio. The kinetics of filling the cell monolayer defect using the “scratch assay” shows that GS in concentrations of 0.5 and 5.0 μg/ml can control the migratory and proliferative properties of L929 cells. Conclusions: The effect of gramicidin S on the morphometric parameters of cells depends on the concentration of the peptide and the cell status in the culture. GS corrupts the adhesive properties of L929 fibroblasts in monolayer cell culture and the rate of cell monolayer formation. Cells at the stage of attachment and monolayer formation were most sensitive to non-lytic concentrations of GS. Inhibition of the adhesive properties of connective tissue cells by gramicidin S is a new non-canonical effect of a known antimicrobial drug, which may indicate the possibility of using gramicidin S as an anti-neoplasm agent.

N. M. Alabedalkarim

V. P. Berest

N. M. Moiseieva

G. A. Bozhok

T. P. Bondarenko

The antimicrobial peptide gramicidin S alters proliferation and inhibits adhesion of L929 cell line fibroblasts

抗菌肽短杆菌肽S改变L929细胞系成纤维细胞的增殖并抑制其粘附

涉及主题	物理化学量子力学生物计算机科学材料科学生物化学有机化学遗传学工程类纳米技术光学
出版信息	出版商: V N Karazin Kharkiv National University，出版周期: ，期刊类型: journal，开源期刊: 是
基本数据	创刊年份: 2019，原创研究文献占比: 0.00%，自引率:N.A.， Gold OA占比: 0.00%
平均审稿周期	网友分享经验：12 Weeks

Biophysical Bulletin

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