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New hexadecylpiperidinium surfactants, containing one or two butylcarbamate fragments, were synthesized. The antimicrobial activity, toxicity, aggregation behavior in aqueous solutions, and solubilization capacity of these surfactants towards the hydrophobic drug ibuprofen were characterized. These surfactants demonstrated a high antimicrobial activity against a wide range of pathogenic bacteria, including both Gram-positive and Gram-negative strains, as well as fungi. By forming mixed-micellar compositions of the cationic surfactant 1-CB(Bu)-P-16 and the nonionic surfactant Brij®35, highly functional and low-toxic formulations were obtained. Furthermore, the transition from mixed micelles to niosomes was accomplished, enhancing their potential as drug delivery systems. Niosomes were found to be less toxic compared to mixed micelles, while also increasing the solubility of ibuprofen in water. The modification of niosomes with cationic surfactants made it possible to increase the stability of the system and improve the solubility of the drug. The data obtained indicate that these new carbamate-containing hexadecylpiperidinium surfactants have significant potential in biomedical applications, particularly in the formulation of advanced drug delivery systems.

An approach to the synthesis of phosphoryl substituted spiro-1,3-dioxolane oxindoles was developed from the base-catalyzed reaction of various isatins with (3-hydroxyprop-1-yn-1-yl)phosphonates. It was found that various aryl-substituted and N-functionalized isatins with the formation of appropriate products with high yields and stereoselectivity when using t-BuOLi are able to react. Cytotoxic activity evaluation suggests that the most significant results in relation to the HuTu 80 cell line were shown by N-benzylated spirodioxolanes. 5-Cloro-N-unsubstituted spirooxindoles exhibit antiaggregational activity exceeding the values of acetylsalicylic acid.

Abstract The work presents core–shell nanoparticles (NPs) built from the novel Cu(I) complexes with cyclic P2N2-ligands (1,5-diaza-3,7-diphosphacyclooctanes) that can visualize their entry into cancer and normal cells using a luminescent signal and treat cells by self-enhancing generation of reactive oxygen species (ROS). Variation of P- and N-substituents in the series of P2N2-ligands allows structure optimization of the Cu(I) complexes for the formation of the luminescent NPs with high chemical stability. The non-covalent modification of the NPs with triblock copolymer F-127 provides their high colloidal stability, followed by efficient cell internalization of the NPs visualized by their blue (⁓450 nm) luminescence. The cytotoxic effects of the NPs toward the normal and some of cancer cells are significantly lower than those of the corresponding molecular complexes, which correlates with the chemical stability of the NPs in the solutions. The ability of the NPs to self-enhanced and H2O2-induced ROS generation is demonstrated in solutions and intracellular space by means of the standard electron spin resonance (ESR) and fluorescence techniques correspondingly. The anticancer specificity of the NPs toward HuTu 80 cancer cells and the apoptotic cell death pathway correlate with the intracellular level of ROS, which agrees well with the self-enhancing ROS generation of the NPs. The enhanced level of ROS revealed in HuTu 80 cells incubated with the NPs can be associated with the significant level of their mitochondrial localization.

Liposome surface potential effect on cellular uptake and cytotoxicity is evaluated using liposomes, modified with cationic lipid DOTAP, a series of cationic gemini surfactants with two carbamate fragments, and an amphiphilic peptide SSRGD. The surfactants used are novel representatives of the gemini family with improved self-assembling activity coupled with potential biodegradable properties and displayed increasing antibacterial activity and cytotoxicity with the shortening of hydrophobic alkyl tails. The longest alkyl tail surfactant, 14-6-14(Et), was the most biocompatible of the series, which was chosen for liposome modification. Prepared liposomes of various compositions are characterized from morphological and physicochemical standpoints in order to optimize their biocompatibility and stability. The carbamate gemini surfactants were also twice as effective at providing positive charge to liposomes and less toxic compared to DOTAP. On their own, carbamate surfactants were able to increase cellular uptake of liposomes by 190%. The mixed composition of 14-6-14(Et) surfactant and SSRGD amphiphilic peptide was the most readily absorbed formulation among different tested neutral, cationic and RGD-modified liposomes. The comparison between the cellular uptake promotion is conducted as to what is the most selective and efficient approach to enhance lipid nanoparticle uptake by cancerous cells.

Air‐stable cyclometalated palladium(II) complexes with benzamide ligands were synthesized in high yields and characterized by X‐ray diffraction analysis, CVA, 1H NMR, 13C NMR spectroscopy, MALDI‐MS, and ESI‐MS. The electrochemical oxidation of the complexes is reversible in the presence of a quinoline substituent in the ligand and gives Pd (III) species that do not undergo reductive elimination and are detectable by ESR spectroscopy. The complexes showed high cytotoxicity against cervical cancer (M‐HeLa) and duodenal adenocarcinoma (HuTu 80), a human mammary ductal adenocarcinoma line (MCF‐7) and a human lung carcinoma cell line (A549). The possibility of generating reactive oxygen species in solution (such as OH−radicals), which can be responsible for the antitumor activity of the studied complexes, using the ESR method was shown. [ABSTRACT FROM AUTHOR]

An approach to the synthesis of phosphoryl substituted spiro-1,3-dioxolane oxindoles was developed from the base-catalyzed reaction of various isatins with (3-hydroxyprop-1-yn-1-yl)phosphonates. It was found that various aryl-substituted and N-functionalized isatins with the formation of appropriate products with high yields and stereoselectivity when using t-BuOLi are able to react. Cytotoxic activity evaluation suggests that the most significant results in relation to the HuTu 80 cell line were shown by N-benzylated spirodioxolanes. 5-Cloro-N-unsubstituted spirooxindoles exhibit antiaggregational activity exceeding the values of acetylsalicylic acid. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance to modern antibiotics stimulates the search for new ways to synthesize and modify antimicrobial drugs. The development of synthetic approaches that can easily change different fragments of the molecule is a promising solution to this problem. In this work, a synthetic approach was developed to obtain multivalent thiacalix[4]arene derivatives containing different number of amine and hydroxyl groups. A series of macrocyclic compounds in cone, partial cone, and 1,3-alternate stereoisomeric forms containing -NHCH2CH2R (R = NH2, N(CH3)2, and OH) and -N(CH2CH2OH)2 terminal fragments, and their model non-macrocyclic analogues were obtained. The antibacterial activity against Gram-positive (Staphylococcus aureus, Bacillus cereus, and Enterococcus faecalis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains and cytotoxicity of the obtained compounds were studied. Structure–activity relationships were established: (1) the macrocyclic compounds had high antibacterial activity, while the monomeric compounds had low activity; (2) the compounds in cone and partial cone conformations had better antibacterial activity compared to the compounds in 1,3-alternate stereoisomeric form; (3) the macrocyclic compounds containing -NHCH2CH2N(CH3)2 terminal fragments had the highest antibacterial activity; (4) introduction of additional terminal hydroxyl groups led to a significant decrease in antibacterial activity; (5) the compounds in partial cone conformation had significant bactericidal activity against all studied cell strains; the best selectivity was observed for the compounds in cone conformation. The mechanism of antibacterial activity of lead compounds with terminal fragments -NHCH2CH2N(CH3)2 was proved using model negatively charged POPG vesicles, i.e., the addition of these compounds led to an increase in the size and zeta potential of the vesicles. The obtained results open up the possibility of using the synthesized macrocyclic compounds as promising antibacterial agents.

The creation of mitochondria-targeted vector systems is a new tool for the treatment of socially significant diseases. Phosphonium groups provide targeted delivery of drugs through biological barriers to organelles. For this purpose, a new class of alkyl(diethylAmino)(Phenyl) Phosphonium halides (APPs) containing one, two, or three diethylamino groups was obtained by the reaction of alkyl iodides (bromides) with (diethylamino)(phenyl)phosphines under mild conditions (20 °C) and high yields (93–98%). The structure of APP was established by NMR and XRD. A high in vitro cytotoxicity of APPs against M-HeLa, HuTu 80, PC3, DU-145, PANC-1, and MCF-7 lines was found. The selectivity index is in the range of 0.06–4.0 μM (SI 17-277) for the most active APPs. The effect of APPs on cancer cells is characterized by hyperproduction of ROS and depolarization of the mitochondrial membrane. APPs induce apoptosis, proceeding along the mitochondrial pathway. Incorporation of APPs into lipid systems (liposomes and solid lipid nanoparticles) improves cytotoxicity toward tumor cells and decrease toxicity against normal cell lines. The IC50s of lipid systems are lower than for the reference drug DOX, with a high SI (30–56) toward MCF-7 and DU-145. APPs exhibit high selective activity against Gram-positive bacteria S. aureus 209P and B. segeus 8035, including methicillin-resistant S. aureus (MRSA-1, MRSA-2), comparable to the activity of the fluoroquinolone antibiotic norfloxacin. A moderate in vivo toxicity in CD-1 mice was established for the lead APP.

This research is based on the concept that mitochondria are a promising target for anticancer therapy, including thatassociated with the use of oxidative phosphorylation blockers (mitochondrial poisons). Liposomes based on L-α-phosphatidylcholine (PC) and cholesterol (Chol) modified with cationic surfactants with triphenylphosphonium (TPPB-n, where n = 10, 12, 14, and 16) and imidazolium (IA-n(OH), where n = 10, 12, 14, and 16) head groups were obtained. The physicochemical characteristics of liposomes at different surfactant/lipid molar ratios were determined by dynamic/electrophoretic light scattering, transmission electron microscopy, and spectrophotometry. The hydrodynamic diameter of all the systems was within 120 nm with a polydispersity index of no more than 0.24 even after 2 months of storage. It was shown that cationization of liposomes leads to an increase in the internalization of nanocontainers in pancreatic carcinoma (PANC-1) and duodenal adenocarcinoma (HuTu 80) cells compared with unmodified liposomes. Also, using confocal microscopy, it was shown that liposomes modified with TPPB-14 and IA-14(OH) statistically better colocalize with the mitochondria of tumor cells compared with unmodified ones. At the next stage, the mitochondrial poison rotenone (ROT) was loaded into cationic liposomes. It was shown that the optimal loading concentration of ROT is 0.1 mg/mL. The Korsmeyer–Peppas and Higuchi kinetic models were used to describe the release mechanism of ROT from liposomes in vitro. A significant reduction in the IC50 value for the modified liposomes compared with free ROT was shown and, importantly, a higher degree of selectivity for the HuTu 80 cell line compared with the normal cells (SI value is 307 and 113 for PC/Chol/TPPB-14/ROT and PC/Chol/IA-14(OH)/ROT, respectively) occurred. It was shown that the treatment of HuTu 80 cells with ROT-loaded cationic liposomal formulations leads to a dose-dependent decrease in the mitochondrial membrane potential.

Cooperation between the regions of the Volga Federal District and the territories of the upper and middle reaches of the Yangtze River of the People’s Republic of China is one of the tools for activating multifaceted Russian-Chinese relations. The creation of a Sino-Russian cooperation mechanism through the Volga — Yangtze Format is of great importance for promoting the development of economic and trade exchanges between the two states, as well as the formation of points of contact in the humanitarian sphere. The similarity of geographical features of these regions is a good basis for the exchange of experience in solving economic, environmental and humanitarian problems of the development of territories located along major waterways.Aim. The purpose of the work is to identify the main vectors of possible development of cooperation and ways to overcome the problems arising in this cooperation by analyzing the intensity of interregional cooperation between Russia and China in the Volga — Yangtze format.Tasks. To analyze program documents and mass-media materials in terms of coverage of the implementation of Sino-Russian projects in the Volga-Yangtze format. To carry out a quantitative analysis of existing joint projects with China in the Volga Federal District. To identify the “growth points” of further economic cooperation between Russia and China in the Volga — Yangtze format.Methods. Empirical research methods, search and analysis of information from mass media, analysis and comparison of data, comparison and generalization were used in the work.Results. By studying the current state of the economic component of Russian-Chinese cooperation in the Volga — Yangtze format, it was possible to identify the difficulties existing in cooperation between the two sides, which could be purposefully solved if the effectiveness of local cooperation was strengthened.Conclusions. At the present stage, there are some obstacles to the effective development of cooperation between the regions of the Volga Federal District and the territories of the upper and middle reaches of the Yangtze River of the People’s Republic of China in the Volga — Yangtze format, such as difficulties in the macroeconomic situation in Russia, the weakness of the foundation of regional cooperation, the need for an effective coordination mechanism at the regional level, as well as clear schemes of financial and tax support. In addition, based on the geographical features of the regions and the reliance of regional economies on water resources, the development of environmental cooperation in the Volga — Yangtze format would be a progressive format of cooperation.

Data for ongoing and completed clinical trials (Phases I-III) were extracted from the European Union Clinical Trials Register for five EU-EECs (Bulgaria, Hungary, Poland, Romania and Slovakia) (from January 1, 2012 to September 30, 2022). Based on the almost 11-year period Poland (n = 4134) and Hungary (n = 3845) represent the largest share of trials, with over 250–300 ongoing and completed clinical trials a year. Bulgaria (with a population of 7 mill. inhabitants) has a lower number of completed and ongoing trials (n = 2049) versus Poland and Hungary, which, however, have much larger populations (Poland − 38 mill., Hungary − 9.8 mill.). Slovakia (5.5 mill. inhabitants), has 67% fewer ongoing and completed clinical trials (n = 1374) than Poland, while Hungary and Bulgaria also have more trials than Slovakia (64% and 33% respectively). The prevalence of trials in all EEC countries was calculated per 100,000 inhabitants, where Hungary (n = 39) ranks first, while Bulgaria (n = 29) is ahead of Slovakia (n = 25), Poland (n = 11) and Romania (n = 5). The ongoing and completed clinical trials conducted in the ten EU-EECs (n = 19030) have shown remarkable expansion over the past decade, accounting for a large share (26.3%) of all EU-wide trials (n = 72215) for the referenced period. The leader of the western EU countries, in terms of trials per 100,000 inhabitants is Denmark (n = 56) followed by Belgium (n = 44), Austria (n = 33), Finland (n = 30) and the Netherlands (n = 30). These results demonstrate that the number of completed and ongoing trials does not correspond to the size of a country’s population.

Amphiphilic calix[4]resorcinarenes are a class of macrocyclic compounds with broad potential utility including nanomedicine. Here the synthesis of new carboxybetaine and carboxybetaine ester calix[4]resorcinarene bearing 4-(dodecyloxy)phenyl groups on the lower rim is presented. The compounds were characterized by 1H-NMR, 13C-NMR, 2D NMR, IR, ESI and elemental analysis. The critical association concentration values are 1.00 × 10−5 and 1.18 × 10−5 mol·L−1 for carboxybetain and ester, respectively. The hemolytic activity of the macrocycles and their cytotoxicity against normal (WI-38, Chang liver) and tumor cells (M-HeLa) are also estimated.

The Asia-Pacific region today represents an example of deep regional economic integration. This was largely facilitated by the creation of the TRANS-Pacific Partnership. The undisputed advantages of the Trans-Pacific Partnership are the following: opening markets to all member countries, unifying trade rules, removing obstacles to financial cooperation, creating a favorable investment climate and new guarantees to protect small and medium-sized businesses. The analysis of historical stages of creation and development of a such kind of regional association allows us to trace the evolution of economic integration processes and assess the effectiveness and attractiveness of this type of integration. The study of the specifics of the origin of such a large integration Association in Asia is of interest from the point of view of searching for new “growth points” for integration associations in the Eurasian region and in particular in the post-Soviet space.

The autonomy of the Aland Islands within Finland implies a system of self-government in a certain area within the borders of a sovereign state. The Aland Islands have an ethnic and cultural identity and receive powers for internal administration as part of the state. The autonomy of the Islands gives them the ability to solve internal problems, while the state remains responsible for foreign policy, security, etc. All this is made possible by the Aland autonomy Act, which came into force in 1993 and was confirmed by the Finnish Constitution. The act regulates almost all issues of self-government of the Islands. At the same time, the Aland Islands can be classified as a federacy, which indicates a special Federal relationship within a unitary state. Domestic cooperation between the Finnish government and the Aland Islands is based on a formal bilateral non-hierarchical partnership.