This work continues our study of graphene oxide nanoparticles. Our research group previously developed a modified method for producing highly oxidized graphene oxide, which forms stable dispersions in aqueous solutions at concentrations up to 9 g & centerdot;L-1. This article examined the effect of oxidation time (1, 2, 3 and 4 h) on the functional composition of the graphene oxide surface, the size and aggregative stability of nanoparticles in aqueous dispersions, and the hemocompatibility and cytotoxicity of the resulting nanomaterials.

Novel 4-(purin-6-yl) piperazin derivative was designed and synthesized as potential AKT1 inhibitor. The interaction pattern between the compound and the enzyme's active site was thoroughly examined using molecular dynamics simulations. Following the initial screening for biological activity, (4-(purine-6-yl)piperazine-1-yl)(benzofuran-2-yl)methanon was chosen as a leader molecule. An extended biological activity profile was obtained for this compound, including its effect on AKT1 activity inhibition and the expression of various markers in myeloid cell lines, as well as the cytotoxicity. It was demonstrated that the lead compound decreased the percentage of Mono-Mac-1 cells from 89.4 ± 0.7% in the control to 41.3 ± 6.2%. For the percentage of PD-L1 checkpoint on cells, it was 96.0 + 1.8% in the control and 36.0 ± 2.9% after the addition of lead compound and for TIM-3, 70.0 ± 1.5% in the control and 9.0 ± 1.1 after the addition of lead compound. According to obtained data on biological activity it is possible to conclude that discovered compound is a potent AKT1 inhibitor downregulating the expression of multiple checkpoints molecules in myeloid cell lines. The paper also presents a scalable method for synthesizing the target compound without application of expensive chromatographic purification of intermediates and the final product. The resulting compound was identified using modern physicochemical analytical methods.

We study the physicochemical and biological properties of water-soluble adducts of fullerene C70 with l-methionine (C70-Met, C70(C5H11NO2S)3) and l-cysteine (C70-Cys, C70(C3H7NO2S)3). The adducts were characterized using 13C NMR, IR, and UV spectroscopy, elemental analysis, and HPLC. The measured physicochemical properties included temperature and concentration dependence of density, viscosity, refraction, electrical conductivity, surface tension of aqueous solutions, solubility in binary systems (C70-Met-H2O and C70-Cys-H2O) and ternary systems (C70-Met-NaCl-H2O and C70-Cys-NaCl-H2O), as well as determination of the partition coefficient in an n-octan-1-ol-water system. In addition, investigation of binding to human serum albumin and DNA was conducted as well as antiradical activity in the model reaction with a stable 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) was studied.

AIMS:This study aimed to develop a novel aziridine-1,3,5-triazine derivative combining DNA-alkylating aziridine rings with a benzimidazole-containing fragment associated with PARP-related chemotypes. MATERIALS AND METHODS:The synthesis of target (4,6-di(aziridin-1-yl)-N-(2-(4-((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)ethyl)-1,3,5-triazin-2-amine (7) was achieved through a multi-step approach, involving the synthesis of 2-methyl-1-(prop-2-yn-1-yl)-1H-benzo[d]imidazole (3) and subsequent click chemistry reaction with N-(2-azidoethyl)-4,6-di(aziridin-1-yl)-1,3,5-triazin-2-amine (6). Protein modeling, docking and molecular dynamics were performed using the Schrödinger suite. Compound 7 was evaluated for cytotoxicity in vitro (HCT-116, U87, HeLa, A549 and ECV304 cell lines) by MTT assay, genotoxicity in HCT-116 cells by DNA-comet assay, and in vivo in A549 and HCT-116 xenografts in immunodeficient BALB/c Nude mice. RESULTS:Docking/MD suggested a PARP-1 binding mode, with key interactions comparable to established inhibitors such as talazoparib and olaparib. In vitro cytotoxicity assays against HCT-116, U87, HeLa, and A549 cell lines revealed dose-dependent antiproliferative effects, with IC50 values of 14.12, 33.52, 44.60, and 26.4 µM, respectively. In vitro genotoxicity assays showed that incubation of HCT-116 cell line with the compound 7 causes dose-dependent damage to DNA integrity. In vivo, compound 7 inhibited tumor growth in A549 xenografts (up to 75.1%, p < 0.05) and demonstrated dose-dependent activity in HCT-116 xenografts (up to 82.9% TGI at 6 mg/kg, i.v.).

Monomethyl auristatin E (MMAE) is a highly active tubulin inhibitor that induces cell cycle arrest in the G2/M phase and apoptosis. High nonspecific toxicity limits its use in individual form, so MMAE is often used as component of drug delivery systems. Graphene oxide contains functional groups that effectively immobilize MMAE and the targeting ligand, increasing the biocompatibility and antitumor efficacy of MMAE while reducing systemic toxicity.

The article presents a non-model algorithm for calculating the fusibility diagrams of multicomponent systems exclusively from data on the fusibility diagrams of binary subsystems. The first geometric calculation algorithm is based on solving systems of linear equations of liquidus isotherms. The second, thermodynamic calculation algorithm requires only the coordinates of the binary eutectic. The application of both algorithms is demonstrated by the example of fusibility diagrams of ternary quasi-simple salt systems with a common cation and a common anion. There is a convincing agreement between the calculation results the results of the non-model calculation with the available experimental literature data. The proof of the fact that all non-invariant points of various quasi-simple ternary systems (with two identical and one different component) belong to one mono-variant curve is given. Examples of calculations of these mono-variant curves are given and convincing agreement of the non-model calculation with experimental data is demonstrated. A system of transcendental equations has been compiled for calculating the coordinates of ternary eutectic.

This article is devoted to synthesis, identification and complex investigation of biocompatibility for graphene oxide (GO) covalent conjugate with [5-[[4,6-bis(aziridin-1-yl)-1,3,5-triazin-2-yl]amino]-2,2-dimethyl-1,3-dioxan-5-yl]methanol (Diox) cytostatic (GO-Diox). GO was synthesised using a patented modified Hummers and Offeman's method leading to the production of GO enriched with oxygen-containing functional groups (similar to 85 %). Obtained nanomaterial was covalently modified with Diox, after which it was characterised using 13C NMR, Raman, and IR spectroscopy, XRD. Biocompatibility study included investigation of hemocompatibility, antioxidant activity, endocytosis, cytotoxicity. Moreover, the photothermal action of GO-Diox nanoconjugate was performed.

Phosphoinositol-3-kinases (PI3K) may be considered as targets for targeted therapy of tumors. The 1,3,5-triazine core is considered the promising scaffold in antitumor drug development, that affect to various targets in tumor cells. This review examines 1,3,5-triazine derivatives ( s -triazine) with strong inhibitory activity against PI3K kinases. Moreover, the key structural fragments that play a crucial role in binding to the active sites of PI3K are summarized. The prospects of developing bifunctional agents, which simultaneously affect two or more targets within the same or different signaling pathways, are also discussed.

The purpose of the study was to consider isothermal vapor-liquid diagrams of quasi-simple systems and to develop a universal algorithm for the calculation of isothermal vapor-liquid diagrams of these systems independent of the type of valence of the electrolyte, the number of components in the system, and the types of solid solutions. The suggested analogues of the three Gibbs–Konovalov and Gibbs–Roozeboom laws are true when moving along the univariant equilibrium lines on the solubility diagrams of systems with a random number of components. The study did not involve any experiments. The suggested algorithm was applied for the description of solubility (solidliquid) diagrams and vapor-liquid equilibrium diagrams of three- and four-component systems with one, two, or three volatile components. In all the cases, the results of thermodynamic first-principles calculations agreed well with the experimental data presented in the literature. Both the experimental data presented in the literature and the results of the thermodynamic first-principles calculation performed by the authors are also in good agreement with the suggested analogues of the Gibbs–Konovalov and Gibbs–Roozeboom laws

Lichen acids have a wide range of biological activity. Of particular interest are their antiradical properties. Due to their structure, lichen acids are able to effectively neutralize free radicals and protect cells from oxidative stress. However, data on the antioxidant activity of biologically active substances contained in lichens are scarce. At present, about 150 orsinol depsides contained in lichens are known, which makes this class of compounds the most numerous among lichen secondary metabolites. Thus, the study of the antiradical properties of lichen acids is relevant, since this will expand the scope of their biomedical application, in particular, for the treatment of diabetes mellitus, inflammatory diseases, etc. From the results presented in this paper on the study of the antiradical activity of lecanoric, perlatolic, imbicaric, olivetric, divaricate, ancyanic acids in a model reaction with DPPH, it can be seen they poses antiradical activity, comparable with fullerene C60.

The creation of highly effective in low concentrations environmentally friendly biocompatible means with a complex positive effect on plants remains relevant due to the lack of saturation of the market with such compounds. In a series of laboratory, vegetation experiments under controlled conditions and field experiments with phytotest objects (spring barley, wheat, Chinese cabbage and other), we have shown the increase of plants resistance to oxidative stress caused by moisture deficiency in the root-inhabited environment after their treatment at the seed stage or during the vegetative period of development with created by us suspensions based on iron oxide nanoparticles or solutions of water-soluble derivatives of fullerene C60 in previously established most effective concentrations [1, 2]. The treated plants with tested substances solutions showed activation of metabolism, processes of their exchange of matter and energy with the environment, increased transport of the main macro- and microelements to the above-ground part, stabilization of the work of plants antioxidant systems, which together contributed to maintaining their productivity indicators and the quality of the formed plant production at the level of those in the control plants grown in favorable conditions.

Marine organisms such as mussels, barnacles, and sandcastle worms demonstrate robust adhesion in aquatic environments. However, the mechanisms underlying their adhesive capabilities remain incompletely understood, and artificial adhesives with comparable performance have yet to be developed. Notably, most of these organisms achieve strong attachment to various underwater substrates through specialized protein-based structures. As a result, researchers have focused on developing peptide- and protein-based underwater adhesives inspired by these natural organisms in recent decades. This review first summarizes the natural protein-mediated underwater adhesive systems of representative marine organisms. It then provides a comprehensive overview of bio-inspired peptide- and protein-based underwater adhesives. Furthermore, the applications of these adhesives across various fields are discussed. Finally, the challenges and opportunities in the development of underwater adhesive biomaterials are briefly explored.

As a result of a comprehensive study of the physicochemical properties of the C60-l-cysteine aqueous solutions, practically significant results were obtained, which underlie the understanding of the mechanisms of biological action and biocompatibility. It was shown that the adduct of fullerene C60 with l-cysteine is compatible with water and aqueous solutions and at the same time is amphiphilic. Aqueous solutions are strongly associated and, depending on the concentration, associates of various orders are formed up to the micron size; dilute solutions have high negative partial volumes, which indicate a strong structure. The adduct does not exhibit cytotoxicity, possesses antiradical activity, and reversibly binds to human serum albumin. The obtained data demonstrates the complexity of the systems under study and the prospects for their application in medicinal chemistry and biomedical materials science.

Water pollution, particularly industrial wastewater, is a major environmental issue due to its adverse effects. Sustainable wastewater treatment is one of the major challenges of this century, as well as sustainable production of polymer membranes for it. One of alternative methods is the production of polyelectrolyte complex (PEC) membranes based on aqueous phase separation approach. In this work, nanofiltration membranes from PEC of poly(sodium-p-styrenesulfonate) (PSS)/poly(diallyldimethylammonium chloride) (PDADMAC) with improved transport characteristics were developed via salt-dilution induced phase separation for enhanced water treatment from food anionic dyes and heavy metal ions. The improvement was carried out by variation of monomer ratio (40-60 wt% PSS), introduction of graphene oxide (GO, 3-7 wt%) and PSS with lower molecular weight (70 kDa) in PEC, and combination of all optimal modification conditions. The structural features of PEC-based membranes were studied by FTIR, NMR, Raman, XPS spectroscopies, scanning electron and atomic force microscopies, and thermogravimetric analysis. A theoretical analysis using quantum chemical calculations was carried out to confirm the influence of polymer interactions with components on changes in membrane properties. For PEC membranes with PSS/PDADMAC monomer ratio of 40/60, modified with 5 wt% GO and with the introduction of both PSS (70 kDa) with GO, led to more than 3.5 and 5 times higher permeance, respectively, and enhanced rejection compared to the unmodified PEC membrane in nanofiltration of dye and heavy metal ion solutions.

The study presents cryoscopic investigation of binary systems containing adducts of fullerene C-60 with sulfur-containing amino acids C-60(C3H7NO2S)(3) (adduct with L-cysteine, C-60-Cys) and C-60(C5H11NO2S)(3) (adduct with L-methionine, C-60-Met). Excess thermodynamic functions of solution components were calculated using a semi-empirical model Virial Decomposition Asymmetric Model (VD-AS). Adducts of fullerene C-60 with sulfur-containing amino acids were characterized using C-13 NMR, IR and UV/Vis spectroscopy, elemental analysis, and HPLC. Additionally, experimental data on the enthalpy of combustion of fullerene adducts, as well as concentration dependences of particle size distribution and zeta-potentials are presented.

This work is devoted to the study of the physicochemical properties of the water-soluble adduct fullerene C60-l-methionine. The adduct was characterized using 13C solid-state NMR spectroscopy, IR spectroscopy, elemental analysis, UV/vis spectroscopy, and HPLC. The measured physicochemical properties included density, viscosity, refraction, electrical conductivity, speed of sound, surface properties of aqueous solutions, nanoparticle size distribution in water, the molecular dynamics simulation of the association of C60-Met molecules in water and isotonic saline (0.15 M NaCl solutions), the study of solubility in binary C60-Met-H2O and ternary C60-Met-NaCl-H2O systems, as well as their distribution in the n-octan-1-ol-water system.

Human carbonic anhydrase IX (CAIX) plays a key role in maintaining pH homeostasis of malignant neoplasms, thus creating a favorable microenvironment for the growth, invasion, and metastasis of tumor cells. Recent studies have established that inhibition of CAIX expressed on the surface of tumor cells significantly increases the efficacy of classical chemotherapeutic agents and makes it possible to suppress the resistance of tumor cells to chemotherapy, as well as to increase their sensitivity to drugs (in particular, to reduce the required dose of cytostatic agents). In this work, we studied the ability of new CAIX inhibitors based on substituted 1,2,4-oxadiazole-containing primary aromatic sulfonamides, to potentiate the cytostatic effect of gefitinib (selective inhibitor of epidermal growth factor receptor tyrosine kinase domain) under hypoxic conditions. We investigated a combined effect of gefitinib and CAIX inhibitors 4-(3-phenyl-1,2,4-oxadiazol-5-yl)thiophene-2-sulfonamide (1), 4-(5-(thiophene-3-yl)-1,2,4-oxadiazol-3-yl)benzenesulfonamide (2), 4-(3-(pyridin-2-yl)-1,2,4-oxadiazol-5-yl)thiophene-2-sulfonamide (3), and 4-(5-methyl-1,2,4-oxadiazol-3-yl)benzenesulfonamide (4) on gefitinib cytotoxicity, cell proliferation, activation of caspases-3/7, and cell cycle control in human lung adenocarcinoma A549 cells. It was found that the combinations of compounds 1 and 2 with gefitinib suppressed the invasive potential of A549 cells. Compound 1 had the greatest effect and can be considered as a promising candidate for further research.

Introduction. Now, one of the most promising areas for the use of graphene-based materials, in particular graphene oxide, is biomedicine. Due to the wide variety of functional groups and the possibility of chemical modification of graphene oxide, the creation of composite materials for biomedical use is promising. These nanomaterials have a unique structure and properties, which determines their use for creating targeted drug delivery systems, in tissue engineering, bioimaging, as well as for creating new materials with antimicrobial and antiviral properties.The objective was to perform synthesis and identification of graphene oxide and its conjugate with glycine, and to study the biocompatibility of the obtained nanomaterials: the effect on haemolysis and platelet aggregation, genotoxicity and cytotoxicity.Methods and materials. Graphene oxide was synthesized from graphite using the modified Hummers and Offeman method, after which the graphene oxide-glycine conjugate was also obtained. Identification was carried out using nuclear magnetic resonance spectroscopy. Estimation of biocompatibility of the obtained nanomaterials included the study of their hemolytic activity, effect on collagen-induced platelet aggregation, cyto- and genotoxicity.Results. Graphene oxide and its conjugate with glycine were synthesized. Identification with using nuclear magnetic resonance spectroscopy confirmed the structure and composition of the substances. The study of the biocompatibility of the obtained nanomaterials showed the absence of hemolytic activity (the degree of hemolysis did not exceed 2.5% at the studied concentration range); the presence of antiplatelet properties (at C=10–100 mg·ml–1); the absence of geno- and cytotoxicity (graphene oxide at C=0.25–25 mg·L–1 does not affect the viability of HEK293 cells; in turn, the conjugate with glycine at C=100–200 mg·L–1 causes a dose-dependent increase proliferation of HEK293 cells).Conclusion. The study demonstrates that functionalization of the graphene surface with oxygen-containing groups and amino acids leads to increased hemocompatibility, as well as to the production of nanomaterials that do not exhibit genoand cytotoxicity.