A series of alkyl[2-(5-chloro-2-hydroxyphenyl)hex-1-en-1-yl]diphenylphosphonium salts were synthesized based on the predicted lipophilicity (logP). The synthesized salts exhibited high antimicrobial activity against gram-positive bacterial and fungal strains and high activity against the antibiotic-resistant Staphylococcus aureus (MRSA) strains. The most active compounds showed low cytotoxicity against human erythrocytes and liver cells and exhibited high selectivity indices.

Novel 1-phenyl(1-thiophen-2-yl)-4-(diphenylphosphoryl)butane-1,3-diones were synthesized by the Claisen-type condensation of 1-(diphenylphosphoryl)propan-2-one with ethyl phenyl(thiophene-2-yl)carboxylates. The tautomeric equilibrium of diketone moiety of phosphine oxides was investigated by 1H and 13C1H NMR spectroscopy. Two species out of five possible tautomers (diketo and mono-enol) were observed in the solution of 1-phenyl(1-thiophen-2-yl)-4-(diphenylphosphoryl)butane-1,3-diones. The major tautomer was the mono-enol form with content 80–90

Using triterpenoid betulin as an example, a convenient method for the synthesis of 5,6-dihydropyran derivatives containing a nor-triterpenoid fragment at position 4 was proposed. The method involves the reaction of lupane triterpenoids with paraformaldehyde in dioxane in the presence of sulfuric acid. Approaches to the synthesis of triterpene derivatives of 5,6-dihydropyran-2-one and penta-2,4-dienoic acid were developed based on the obtained 4-(3,28-diacetoxy-20,29,30-tri-nor-lupan-19-yl)-5,6-dihydropyran. Triterpene-substituted penta-2,4-dienoic acid heated with triphenylphosphonium triflate formed a quaternary phosphonium salt, which showed cytotoxicity against human cancer cells MCF-7 (breast cancer) and HCT116 (colon cancer) with IC50 4–19 µmol L−1, with its activity against these cell lines being superior to the activity of the comparison drug camptothecin.

Water-soluble ammonium salts were prepared by the reaction of new sterically hindered isatin derivatives with analogues of Girard's reagents. The resulting isatin-3-hydrazones exhibit high antimicrobial and antiaggregation activity with low hemotoxicity. The dependence of physiological activity on the volume of the benzyl substituent was established.

Based on the method developed in this study for obtaining water-soluble PGKCo and PGNaCo, which we had previously synthesized, a pharmacological composition (PC) containing simultaneously the macroelements K and Na, as well as the trace element Co, was obtained for the first time. The effect of polygalacturonates and PC on the viability of cells of tumor lines of various origins was studied in vitro. It was shown that the target products have water solubility, low toxicity (LD50 above 5000 mg kg–1) and selective cytotoxic activity against the tumor cell line of human lung carcinoma A549, breast adenocarcinoma MCF-7 and cervical carcinoma M-HeLa. The results obtained confirm the prospects for further research into water-soluble metal complexes and PC based on pectin biopolymers for the treatment of cancer.

The reactions of 1,1,1,2,3-pentachloro-1-phosphaindene (1) with phenylacetylene and catechol were found to lead to the regioselective formation of the addition product, 1,1,2,3-tetrachloro-1-(2-chloro-2-phenylvinyl)-1-phosphaindene (6), and spirophosphorane, 1,2-bis(2′,3′-dichloro-2H-2λ5-spiro[benzo[d][1,3,2]dioxaphosphole-2,1′-phosphaindene]-2-yl)oxybenzene (13). The hydrolysis of compound 6 proceeds through the intermediate formation of (Z)-2,3-dichloro-1-(2-chloro-2-phenylvinyl)phosphaindene 1-oxide (9) and affords the P—C bond cleavage product, [(Z)-2-chloro-2-phenylvinyl]-(2-[(Z)-1,2-dichlorovinyl]phenylphosphinic acid (10). The structures of compounds 1, 6, and 13 were determined by X-ray diffraction. Compound 6 is the first example of monocyclic phosphoranes containing the phosphorus atom in a nearly ideal trigonal-bipyramidal configuration with an antiapicophilic (diequatorial) arrangement of the five-membered ring at the base. Quantum chemical calculations showed that this structure is favorable due to conjugation effects. Compound 13 has a planar chirality in the crystal (space group P21).

New ammonium hydrazones have been synthesized by the reaction of Girard’s reagents T and P with isatin derivatives that contain various alkyl or geranyl substituents in position 1. A pronounced anti-anthropo- and antiphyto-pathogenic effect of resulting compounds has been revealed. The n-octyl and octadiene derivatives have the highest selectivity for resistant strains of Staphylococcus aureus when there is no negative effect on the hemostasis system. The aggregation and adsorption properties of the compounds have been studied using tensiometry, conductometry, and UV spectroscopy. The found values of the critical micelle concentration of amphiphilic ammonium hydrazones are an order of magnitude lower than those of quaternary ammonium salts.

Currently, there are problems to standardize methods for determining the concentration of nanoparticles and creation of etalon materials for calibrating measured concentrations. Accurate determination of nanoparticle concentration is necessary to assess the maximum dose of administered nanotherapeutics for diagnostics and therapy in vivo, to determine the order of reaction in enzymatic nanoreactors. In addition, this parameter determines biological effects, such as the formation of a protein corona on the outer surface of nanoparticles that precedes nanoparticles’ absorption and internalization in cells. This review discusses the most common methods for determining the concentration of nanoparticles based on direct visualization, using microscopy, light absorption or light scattering, direct counting of nanoparticles, and gravimetry. Results may differ from one method to the other. Thus, the use of a combination of several methods provides more reliable results. The advantages, disadvantages and ways to improve accuracy of results are also presented.

The reaction of 2-R-naphtho[2,3- d ][1,3,2]dioxaphosphinin-4-ones with derivatives of β-dicarbonyl compounds, such as bis(2,2,3,3-tetrafluoropropyl) benzylidene- and 4-bromobenzylidenemalonates, afforded seven-membered heterocycles, 5-oxo-2-R-naphtho[2,3- f ][1,2]oxaphosphepine 2-oxides, with high regioselectivity and stereoselectivity. In all cases, the major diastereomers were isolated and their structures were established by quantum chemical calculations, NMR spectroscopy, and X-ray diffraction analysis. In the crystal structures, the seven-membered heterocycle of the molecules adopts a distorted boat conformation. In solution, the molecules can adopt both a distorted boat conformation and a chair conformation with a similar energy. The process also involves the reversible kinetically controlled formation of spiro phosphoranes, which are gradually transformed into thermodynamically more stable 1,2-oxaphosphepines. The reaction proceeds under mild conditions and leads to the formation of P—C and C—C bonds and the phosphoryl group.

The problem of low efficiency of nanotherapeutic drugs challenges the creation of new alterna- tive biomedical nanosystems known as robotic nanodevices. In addition to encapsulating properties, nanode- vices can perform different biomedical functions, such as precision surgery, in vivo detection and imaging, biosensing, targeted delivery, and, more recently, detoxification of endogenous and xenobiotic compounds. Nanodevices for detoxification are aimed at removing toxic molecules from biological tissues, using a chem- ical- and/orenzyme-containing nanocarrier for the toxicant to diffuse inside the nanobody. This strategy is opposite to drug delivery systems that focus on encapsulating drugs and releasing them under the influence of external factors. The review describes various kinds of nanodevices intended for detoxification that differ by the type of poisoning treatment they provide, as well as the type of materials and toxicants. The final part of the review is devoted to enzyme nanosystems, an emerging area of research that provides fast and effec- tive neutralization of toxins in vivo.

The reaction of bisisatins containing a 1,ω-alkylene, -arylene, or -alkyluracil spacer with ammonium acetohydrazides gave a series of symmetric and asymmetric dicationic isatin-3-acylhydrazones. It was shown that the antimicrobial activity of the new compounds depends on the structure of the spacer and the nature of the substituent in the aromatic fragment. 5-Substituted isatin derivatives, where the heterocyclic fragments are linked by an 9- and 10-carbon alkylene chains, exhibit bactericidal effect against resistant strains of S. aureus at the level of Norfloxacin and the fungal pathogen P. cactorum , which causes plant late blight.

Formation of stable complexes of pectin polysaccharides with Nifedipine hypotensive drug has been shown by IR and UV spectroscopy, stereochemistry of the complexes has been determined, their preparation conditions have been optimized. Features of thermal decomposition of pectin and the prepared complexes with Nifedipine have been studied by TGA/DSC. Obtained results provide scientific foundation to design new water-soluble non-toxic formulation of Nifedipine to expand the use of the drug in medicine.

In order to search for new antibacterial and anticancer agents, the data of amphiphilic quaternary ammonium compounds (QAC) based on natural structures were analyzed and systematized over the past three years in this review. The analysis of publication is considered on the properties of QAS based on heterocyclic and pyridine alkaloids, alkylated phenols, terpenoids and steroids. The relationships between the structure of ammonium salts and their supramolecular self-assembly, biological activity, and cytotoxicity were tried to be revealed. In terms of synthetic ease of chemical modification, availability, biorelevance, and efficacy against strains of bacterial pathogens and antitumor activity, prospects for using natural platforms for extended trials have been identified.

The interaction of bis-isatins containing a 1,-ω-alkylene, arylene, or alkyluracil spacer with ammonium acetohydrazides yielded a series of dicationic isatin-3-acylhydrazones with symmetric and asymmetric structures. It was shown that the antimicrobial activity of the new compounds depends on the structure of the spacer and the nature of the substituent in the aromatic fragment. Derivatives based on 5-substituted isatins, in which heterocyclic fragments are linked by an alkylene chain of 9 and 10 carbon atoms, exhibit a bactericidal effect against resistant strains of Staphylococcus aureus at the level of norfloxacin and the pathogen fungus P. cactorum , which causes plant late blight.

2-R-4,4-Bis(trifluoromethyl)benzo[f][1,3,2]dioxaphosphepin-5-ones containing an endocyclic carbonyl group, when stored or slightly heated, undergo spontaneous intramolecular cyclization into P+–C–O–-bipolar ions containing benzoxaphosphole and oxaphosphethane rings fused along the P–C bond. These ions further dimerize into carbaphosphatrane derivatives with a pentacoordinate phosphorus atom, where the P–C bond is incorporated simultaneously into four-, five-, and six-membered rings. Hydrolysis of the carbaphosphtranes leads to the formation of benzo[d][1,2]oxaphosphole derivatives. The structure of one of the carbaphosphatranes, as well as one of the benzo[d][1,2]oxaphospholes has been proved by X-ray diffraction analysis. Carbon substituents in the carbaphosphatrane occupy apical positions, whereas the more electronegative oxygen atoms are in equatorial positions.

A series of isatin derivatives containing an adenine or theophylline fragment have been synthesized. The corresponding N′-[2-(trimethylammonio)acetyl] and N′-(2-pyridinioacetyl) hydrazones have been found to exhibit neither cytotoxicity nor hemotoxicity. Quaternary salts based on adenine derivatives of 5-methyl- and 5-ethylisatins showed the highest antiplatelet activity which exceeded the activity of acetylsalicylic acid by a factor of 1.5.

The condensation of phenolic isatin derivatives with 1-(2-hydrazinyl-2-oxoethyl)-4-aza-1-azoniabicyclo[2.2.2]octane bromide yielded a series of isatin-3-acylhydrazones containing a monocationic DABCO fragment. New compounds have antimicrobial activity against phytopathogenic bacteria and fungi, as well as a number of anthropopathogenic bacteria and fungi. Salts based on 5-alkylisatins exhibit bactericidal effect against Staphylococcus aureus at a concentration of 15.6 μg/mL.

This work deals with the creation of new multifunctional quaternary ammonium compounds (QACs) on natural isatin scaffold as a new generation of antimicrobial agents. 1-R-isatin-3-acylhydrazones containing quaternized DABCO moieties (Dabco-Is-n) with varying hydrophobicity (R = CnH2n+1, where n = 10, 12, 14, 16, 18) were synthesized. The idea was to combine two bactericidal fragments, presumably with different mechanisms of action, in the structure of self-assembling quaternary ammonium compounds. The self-assembly behavior, solubility properties toward hydrophobic dye Sudan I, antimicrobial activity against gram-positive and gram-negative bacteria, fungi, hemolytic activity, cell toxicity (MTT-test) and in vitro anticoagulant and anti-aggregation activities were investigated. Established by tensiometry, conductometry, dynamic light scattering and UV-spectrophotometry, the value of Dabco-Is-n critical micelle concentration is 10 times lower than for Dabco-n surfactants. That is, Dabco-Is-n self -assemblies are responsible factor for the manifestation of antimicrobial activity. Dabco-Is-12 was found to be largely blood biocompatible with low toxicity and low hemolysis (IC50 and HC(50 )are >= 100 lM, neg-ligible coagulation) and with high biological activity against methicillin-resistant strains of S. aureus MRSA-1 and MRSA-2 (MIC = 3.5 and 7.0 mu M, respectively) and high solubilization capacity toward hydrophobic dye (Sudan I). Moreover, it forms hydrogen-bonds with drugs (niclosamide and piperine) and displays a good selectivity index toward fungi Candida albicans ATCC 10231. Such new nontoxic Dabco-Is-n biocides with antibacterial and antifungal effects have a good potential for medical applications. (C) 2022 Elsevier B.V. All rights reserved.

Magnesium complexes based on sodium polygalacturonate and pectinate were prepared and characterized. The conditions of complex formation were optimized and the immunomodulatory activity of the complexes was studied in vivo for the first time. The pectin complexes with magnesium ions decrease the immunosuppressive effect of the cyclophosphamide cytostatic, associated with a decrease in the number of immune cells in the blood (leukopenia) after administration of cyclophosphamide, and promote restoration of the white blood cell count in blood and the ratio of their subpopulations, i.e., the complexes exhibit immunomodulatory properties.