Tumor-associated macrophages (TAMs) are immune cells that perform essential roles within the tumor microenvironment. These macrophages can change their functional characteristics in response to local environmental cues, switching between an M1-like phenotype (anti-tumor) or an M2-like phenotype (tumor-promoting). Unfortunately, TAMs are largely polarized into the M2-like phenotype, contributing to tumor growth and immunosuppression. Understanding and modulating TAM polarization is essential in cancer research and therapy. Therefore, strategies to modulate and reprogram M2 macrophages towards an M1-like phenotype have been explored as potential approaches to boost anti-cancer immune responses and enhance the effectiveness of cancer therapies.

One of the significant challenges in targeting M2 macrophages is the need for specific and high-affinity targeting ligands that can distinguish them from the anti-tumor M1-like TAMs. Recently, Pun et al. reported that the polypeptide M2pep (YEQDPWGVKWWY) preferentially binds to M2 macrophages; however, further studies are needed. In order to investigate the selectivity of M2pep towards M2-like TAMs using fluorescence-based techniques, we report here the synthesis and characterization of the M2pep substrate labelled with a fluorophore (Rhodamine B). This peptide comprising a 12-amino acid sequence with three additional amino acids (GGG) was synthesized and coupled to Rhodamine B at its N-termini by microwave-assisted solid phase synthesis, using the Fmoc strategy. The structure of the labelled peptide was confirmed by NMR, UV-Vis and fluorescence spectroscopy and mass spectrometry.

Based on (5Z,9Z)-tetradeca-5,9-diene-1,14-dioic acid previously undescribed polyether aromatic macrodiolides were synthesized in good yields (53-67%). The cytotoxicity of the resulting macrocyclic compounds in vitro against tumor Jurkat, K562, conditionally normal Hek293 cell lines and normal fibroblasts was assessment carried out. The ability of the most active macrodiolide to induce apoptosis towards Jurkat cells and influence the cell cycle was studied.

Tetraazatricyclanes containing two boron atoms in the molecular framework were synthesized for the first time by the heterocyclization reaction of tetraamines with tetrakis(dimethylamino)diborane. Tetrakis(dimethylamino)diborane is a new starting reagent in the synthesis of polyheterocyclic compounds that may be of interest as cytotoxic agents.

New hybrid fullerene C60 derivatives with five norbornadiene fragments bound to a fullerene core by several methylene groups were synthesized for the first time. Subsequent photoirradiation of these C60 fullerene derivatives leads to only partial (up to 20%) opening of double bonds in norbornadiene fragments to form quadricyclane substituents. It is assumed that the resulting C60 fullerene derivatives can be the basis to create high-energy materials.

A potentially dianionic symmetric bisthiosemicarbazone ligand H₂L^Et has been prepared by a condensation reaction between two equivalents of 4-N-ethyl-3-thiosemicarbazide and one equivalent of 4,4’-methylenebis(acetophenone). The crystal structures obtained from solvents with different donor ability were studied. Recrystallization of H₂L^Et from methanol and dimethylsulfoxide allows the isolation of single crystals suitable for X-ray diffraction studies of [H₂L^Et] 1 and [H₂L^Et]·CH₃SOCH₃ 2, respectively. This study shows that the solvent does not affect the macrostructure but influences the microstructure of the ethyl-substituted bisthiosemicarbazone ligand H₂L^Et.

Introduction

The scientific community faces the challenge of creating complex organic compounds from simple substratesusing environmental criteria, safety and efficiency ofthe synthetic procedures. Well-known method in this regard, particularly in the synthesis of azaheterocycles is Biginelli multicomponent reaction, which allows to vary the nature of the reagents involved in the reaction, and the conditions of its implementation.

The combined experimental and theoretical study of the spectral characteristics of molecular systems is one of the most important modern tools for solving problems of current organic chemistry. Such an approach is relevant for a correct description of the composition and structure of the reaction mixtures of biologically active compounds, especially when it comes to mobile tautomeric equilibrium.

Experimental details

Chromenopirazolopyrimidinone (CPP) was synthesized using microwave radiation in the absence of solvent by a multicomponent reaction of 4-hydroxy-2H-chromen-2-one with 5-amine-1H-pyrazole and benzaldehyde. CPP was characterized by a set of spectroscopic methods (FTIR, UV-Vis, NMR, LDI-MS). Decomposition of UV-Vis spectra was performed by component analysis implemented in MILCA algorithm.

Results and Discussion

CPP exists as a mixture of tautomeric forms, the structure of which was examined by means of an integrated approach using spectroscopic methods and quantum chemistry. As was shown by MILCA algorithm, UV-Vis spectra obtained in different solvents of various polarity contain bands of all tautomeric forms. Decomposition of the absorption spectra of CPP in various solvents on the individual components of the absorption showed the presence of two tautomers. The molar ratios of tautomeric forms depend on polarity of solvent used.

One of the most important characteristics that is of great importance for the development of biomaterials based on hyaluronic acid (HA) and its chemically modified derivatives is resistance to hyaluronidases (HA-ase) responsible for the degradation of HA macromolecules. In this work, samples of phosphorylated (HA-P) low and high molecular weight HA (43 kDa and 0.5-0.7 MDa) were obtained by conventional stirring of HA/P2O5 mixtures at different molar ratios (1:0.2, 1: 0.5, 1:1 and 1:2) and exposed to bovine testicular HA-ase (60 or 600 МЕ/mL, [HA]=4 mg/mL of citrate buffer, pH 6.3, 16-18 h). It was found that biodegradability of the HA-P samples obtained at the ratio of 1:0.2, 1: 0.5, and 1:1 was at the level of native HA or even exceeded the HA biodegradability. Only samples obtained at a HA/P2O5 ratio of 1:2 showed resistance to HA-ase: their biodegradability was 13-54% lower compared to that of native HA.

The synthesis of aldehyde-pap as a key precursor through a triple reaction sequence: diazotization-addition/CuAAC/oxidation by using 4-methyl-N³-[4-(pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine as the starting material is described. Furthermore, a molecular docking study was conducted to assess the potential of these compounds as possible ABL kinase inhibitors. Finally, leveraging our in silico investigations, we introduce a small virtual library of compounds Imatinib analogs, which will aid in identifying the optimal candidates for further in vitro experimentation.

The adverse health effects caused by specific anions underscore the importance of easy and straightforward anion recognition. Excessive levels of anions such as cyanide or nitrate can disturb physiological processes, leading to health problems. For instance, cyanide ions (CN⁻) are highly toxic, disrupting cellular respiration by inhibiting vital enzymes. However, cyanide is widely used in various industrial processes, including gold and silver extraction, metal electroplating as well as in the production of paper, textiles, and nitrile. Therefore, the selective and sensitive detection of cyanide ions is essential for human well-being, environmental preservation, and the advancement of scientific and medical knowledge in the context of cyanide exposure.

Nowadays, optical chemosensors designed for anion detection are highly attractive for biological and environmental applications because of their simplicity, cost-effectiveness, and real-time response, without requiring advanced equipment. Cyanine-based probes, in particular, offer numerous advantages as optical chemosensors, including high sensitivity, tunable optical properties, and biocompatibility, making them valuable tools in analytical chemistry and biosensing applications.

Following our previous work focused on the synthesis of a sulfo-cyanine dye and its evaluation as an optical chemosensor for cations, we now report its chromo-fluorogenic ability for anion detection. Chemosensing studies revealed that this compound exhibited remarkable selectivity and sensitivity for CN⁻ in acetonitrile solution, with a marked colour change from cyan to colourless and the fluorescence emission was switched off. The detection limit was estimated to be as low as 0.45 μM, and the binding mode was studied using NMR techniques.

In the present research, bis(Pyridinium-4-carbaldehyde thiosemicarbazone) hexafluorophosphate, nitrate (1) have been prepared by protonation of 4-Formylpyridine thiosemicarbazone (4fpytsc, 2). The compound 1 and the starting thiosemicarbazone have been well characterized and their molecular and crystal structures were studied by single-crystal X-ray diffraction. The supramolecular assembly of each crystal is also analyzed and discussed.