Vol 50, No 7 (2016)

This review addresses progress in recent years in the study of antitumor antibiotics of the aureolic acid group.

X-ray diffraction analysis studies showed that in a mixture of HCl, AcOH, and H₂O, hydrolysis of several 3-[3-(1-arylethylcarbamoyl)-4-hydroxy-2-oxo-1,2-dihydroquinolin-1-yl]propanenitriles proceeded by an anomalous pathway to yield 4-hydroxy-1-(2-carboxyethyl)-2-oxo-1,2-dihydroquinoline-3-carboxylic acid. These experiments showed that methylation of the methylene bridge separating the amide nitrogen atom and the aromatic nucleus led to a drop in activity. At the same time, hydration of quinolinylpropanenitriles to the corresponding propanamides was seen as a successful approach to chemical modification enhancing analgesic properties.

Aseries of 5-(heterylmethylene)hexahydropyrimidin-2,4,6-triones was synthesized and their activities against Staphylococcus aureus, Bacillus subtilis, and Escherichia coli were assessed, with determination of minimum inhibitory concentrations.

A series of novel sulfonylamino pyrrolidine derivatives were synthesized, characterized and evaluated for their antimicrobial activity. All compounds exhibited moderate activity against the microorganisms tested. The compounds were evaluated in silico for their ability to inhibit epidermal growth factor receptor (EGFR). Docking in silico demonstrated that the sulfonylamino pyrrolidine derivatives represent a new class of EGFR inhibitors and bind at the ATP binding pocket of the tyrosine kinase domain of EGFR. The free energy of binding and inhibition constant (k_i) of the docked compounds were evaluated.

Studies of the actions of niclosamide against tumor cells and normal human cells (human embryo kidney cells and pulmonary embryo fibroblast cells) showed higher levels of cytotoxic activity against tumor cells, including melanoma (the Mel-8, Mel-10, MS lines) and colorectal cancer (the Caco-2, COLO 320 HSR, and SW827 cells). Niclosamide was shown to have a high level of cytotoxic activity against cells with the multidrug resistance phenotype due to high levels of expression of MDR1 protein on the plasma membrane (the Mel-8 and MCF-7Adr lines). The proportion of tumor stem cells (TSC) was measured by flow cytometry as the proportion of cells forming side populations (SP). Niclosamide was found to act on TSC cells either more effectively (colorectal cancer line SW 837, (decreases in SP fraction size) or with the same effectiveness as the main population of tumor cells (SP fraction size unaltered).

In this study, iron oxide magnetic nanoparticles (MNPs) were synthesized and their surfaces were functionalized with various polymers. Then, ibuprofen was attached and the kinetics of drug release from this system at various temperatures and pH was studied. The nanoparticles were synthesized by the Massart co-precipitation method. Their surfaces were functionalized with chitosan, PEG or dextran. The concentration of released ibuprofen was measurement in vitro by spectrofluorometric methods. The mechanism of drug release from the carriers was analyzed in the Korsmeyer – Peppas model. According to the results, the amount of ibuprofen released depends on the type of material by which MNPs are coated. Nanoparticles coated with dextran seem to be the most promising material for ibuprofen release. In the Korsmeyer – Peppas model, the values of diffusion exponent n characterize the mechanism of drug release. The values obtained for dextran and PEG point to the Fickian diffusion, while the diffusion mechanism for chitosan is anomalous. These results show the possibility of practical use of the material synthesized in living organisms.

A complex of isoflavonoids containing more than 78% isoflavone and pterocarpan glycosides was obtained from an alcoholic extract of the roots of the Amur maackia, a far eastern relict tree (Maackia amurensis Ruper et Maxim.). This complex contained the 7-O-gentiobiosides of daidzein, genistein, afromosin, pseudobaptigenin, formononetin, and 5-O-methylgenistein, the 3-O-gentiobiosides of maackiain and medicarpin, the compounds daidzin, and genistein, 7-O-primverosylformononetin, and the novel 7-O-primverosylpseudobaptigenin. Studies using a model of toxic hepatitis induced by poisoning of rats with carbon tetrachloride addressed the effects of the complex of isoflavonoids on the state of carbohydrate metabolism in the rat liver. Administration of this complex to animals with CCl₄ hepatitis decreased the activity of marker enzymes for cytolysis and the specific weight of the liver, promoted maintenance of the blood glucose and oxidized nicotinamide coenzyme (NAD⁺) levels, and normalized pyruvate and lactate levels in the animals’ livers. The isoflavonoid complex extracted from Maackia amurensis was more effective in restoring the reactions of liver carbohydrate metabolism (gluconeogenesis, Krebs cycle) than the reference hepatoprotector Legalon^®.

We present here the results of our studies of the in vitro antibacterial and antifungal activity of dioxidine (hydroxymethylquinoxaline dioxide) against 32 strains of bacteria and fungi. Dioxidine was found to exhibit high levels of activity against two of the anaerobic bacteria tested: Peptostreptococcus anaerobius and Bacillus fragilis (MIC ≤ 0.125 μg/ml). Dioxidine was moderately active against Gram-negative bacteria (MIC 8 – 64 μg/ml) apart from Pseudomonas aeruginosa (MIC = 1024 μg/ml) and Stenotrophomonas maltophila (MIC = 512 μg/ml). Dioxidine inhibited the growth of Gram-positive bacteria but at higher concentrations than for Gram-negative bacteria (MIC 64 – 1024 μg/ml). Dioxidine at 1024 μg/ml delayed the growth of yeast-like fungi of the genus Candida (C. albicans). The mold fungus Aspergillus niger was resistant to dioxidine (MIC > 4096 μg/ml).

Current aspects of the technology used to create matrix formulations ar presented. The main types of matrix are described depending on their behavior in the body; matrix-forming ingredients available on the Russian market are reviewed and the main principles determining their selection are discussed, along with the main technological principles underlying the preparation of matrix formulations. Technical factors affecting release of active substances from matrixes are addressed. Experimental data on release from matrix tablets based on composite polymer carriers are presented.

A method for the analysis of microbial “growth curves” by real-time recording of changes in the impedance electrical conductance of the medium from multiple samples in parallel is described; these changes arise from metabolic processes taking place in the test microorganisms in the samples. Results obtained from practical application of the impedance biotesting method for analysis of the antibacterial activity of the aseptic agent chlorhexidine bigluconate are presented, along with results obtained using solutions of a catholyte and an anolyte obtained by processing 1% NaCl and Na₂SO₄ solutions in a specially constructed 2-liter eletrolyzer for 25 min with a current of I = 7 A and a voltage of V = 28 V.