Introduction. Irrational use of antimicrobial drugs, chemical and biological agents leads to the emergence and spread of resistance in microorgan-isms. Therefore, there is an increasing need for the search and development of new antimicrobial compounds. Dihydroxanthone derivatives, which have a wide spectrum of action, are one of the promising groups of antimicrobial substances. New derivatives of 4,4a-dihydroxanthone were obtained at the St. Petersburg State Chemical and Pharmaceutical University (SPCFU) at the Department of Organic Chemistry. Synthetic 4,4a-dihydroxanthones are structurally similar to antimicrobial xanthones of natural origin – fomalevones A and C. Therefore, 4,4a-dihydroxanthones are promising compounds for the creation of new antimicrobial substances. Purpose of the study. To establish the relationship between the chemical structure of the synthesized dihydroxanthones and their antimicrobial ac-tivity and to standardize the active compound. Materials and methods. 20 new derivatives of 4,4a-dihydroxanthone were synthesized. The structure and identity of the compounds was estab-lished using physical and chemical methods of analysis. The antimicrobial activity of these derivatives was studied by double serial dilution method. Quality standards for the most promising compound 5-bromo-7-chloro-4,4-dimethyl-9-oxo-4,4a-dihydroxanthone (a17) were developed. Results. In preliminary studies, we found that 4,4a-dihydroxanthones synthesized in SPCFU have a pronounced effect against gram-positive bacteria. It was found, that the antibacterial activity of 4,4a-dihydroxanthone derivatives depended on their structure. The presence of substituents with acceptor properties led to an increase in activity, while donor substituents reduced the antimicrobial effect of the compounds. 5-Bromo-7-chloro-4,4-dimethyl-9-oxo-4,4a-dihydroxanthone (a17) turned out to be the most active compound, and we carried out its standardization for some indicators. Conclusions. During the study of the antimicrobial activity of the synthesized dihydroxanthones, it was found that they are active against gram-positive bacteria. The antibacterial activity of 4,4a-dihydroxanthone derivatives depends on their structure. Among them, the most active compound was identified – leader a17, which has a pronounced antistaphylococcal effect. Its standardization has been carried out for some indicators.

Исследование посвящено изучению антагонистической активности вторичных метаболитов, выделенных из мицелия штамма Streptomyces cremeus, в отношении фитопатогенных грибов для дальнейшего определения действующих веществ.Высшие актинобактерии имеют большое практическое значение в связи с их способностью продуцировать различные биологически активные вещества, в том числе антибиотики, применяемые во многих отраслях -медицине, ветеринарии, растениеводстве, пищевой промышленности

An impedance technology or conductometric method in microbiological control is an indirect culture method for the determination of microorganisms using measurements of the impedance, i.e., electrical resistance to an alternating current in a growth medium as its chemical composition is transformed by the growth and metabolic activity of microorganisms. Traditional pharmacopoeial methods (double-layer agar method, surface inoculation, submerged cultivation) are used in practice for analysis. The conductometric method and the ATP-luminescent method for determining the total number of microorganisms can be used as alternative methods that significantly reduce the time of analysis and the amounts of consumables. The possibility of using impedance technology (conductometry method) for the determination of the total number of aerobic microorganisms in samples of medicinal plant raw materials with high levels of microbial contamination was examined by us. The aim of the study was to determine the total number of aerobic microorganisms in 1 g (mL) of herbal medicinal raw materials by impedance conductometric and pharmacopoeial cup agar methods. The results from determining the number of aerobic microorganisms using the cup pharmacopoeial and conductometric methods agreed with a correlation coefficient of 0.964.

The “microbiological purity” criterion is an important quality attribute of non-sterile drugs and excipients in the pharmaceutical industry. The impedance conductometry method of microbiological analysis (ICMMA) is based on monitoring of changes in the impedance (resistance to alternating electric current) of liquid growth medium resulting from the living activity of microorganisms contained in the analyzed sample. The aim of this work was to determine the possibility of using ICMMA for determining the total number (TN) of aerobic microorganisms in natural excipients. As a result, the TNs determined by conductometric and pharmacopoeial two-layer agar methods converged with a correlation coefficient of 0.95. This allowed the conductometric method to be recommended as a routine method for determining the TN of aerobic microorganisms when analyzing the microbiological purity of excipients intended for pharmaceutical production.

МНОГОФАКТОРНЫЙ ЭКСПЕРИМЕНТ В ОПРЕДЕЛЕНИИ ОПТИМАЛЬНЫХ ДИАПАЗОНОВ СВЧ-ИЗЛУЧЕНИЯ, АКТИВИЗИРУЮЩИХ РОСТ ДРОЖЖЕЙАнаньева Е.П

 БИОЛОГИЧЕСКИЕ НАУКИ  СТАТЬИ УДК 57.033 ВЛИЯНИЕ РЕЖИМОВ ОБРАБОТКИ СВЧ-ИЗЛУЧЕНИЯ НА ХАРАКТЕРИСТИКИ ДРОЖЖЕВЫХ ОРГАНИЗМОВ Ананьева Е.П., Богданова О

Introduction. Partially hydrogenated derivatives of xanthone, dihydroxanthones, are being intensively studied. They are of interest due to their antimicrobial, antitumor, and antioxidant effects. Many researches are focused on the study of the cytotoxicity of dihydroxanthones and very little information is available on their antimicrobial activity. Therefore, the study of the antimicrobial activity and mechanism of action of new synthetic derivatives of 4,4a-dihydroxanthone is relevant. Preliminary studies have demonstrated that 4,4a-dihydroxanthones are active against gram-positive bacteria and have a pronounced anti-staphylococcal effect. Namely, 5-bromo-4,4-dimethyl-7-chloro-4,4a-dihydroxanthone (BDC-DX) was shown to be the most active derivative.Aim of the study was to determine the possible target of action of the active derivative of BDC-DX in bacterial cells and its acute toxicity.Materials and methods. The method of measuring the intensity of absorption of the crystal violet dye by bacteria cells was used to prove the effect of BDC-DX on the permeability of the cytoplasmic membrane in bacterial cells. The plasma coagulase activity of Staphylococcus aureus was tested under the action of dihydroxanthone to determine the effect of dihydroxanthone on the process of protein synthesis. Plasmid DNA digestion method was used to study the effect of the compound on bacterial DNA. The acute toxicity of BDC-DX was determined by the express method of V.B. Prozorovsky.Results and discussion. BDC-DX increased the permeability of the cytoplasmic membrane of S. aureus. Dihydroxanthone did not directly affect the plasma coagulase activity of Staphylococcus and showed a weak damaging effect on bacterial DNA. The compound induced breaks in plasmid DNA at a very high concentration — 1 mM or 384 pg/ml and higher. BDC-DX is a low-toxic compound (the average lethal dose for oral administration of the compound is 1710 ± 170 mg/kg, the average lethal dose for intraperitoneal administration of the compound is 116.9 ± 13.3 mg/kg).Conclusion. For the first time, in-depth study of the possible mechanism of action of a new synthetic biologically active compound from the group of 4,4a- dihydroxanthones, BDC-DX, was conducted. A likely target of 5-bromo-4,4-dimethyl-7-chloro-4,4a-dihydroxanthone in S. aureus cells is the cytoplasmic membrane. BDC-DX did not affect the process of protein synthesis, namely the activity of the plasma coagulase enzyme. The compound had no pronounced damaging effect on bacterial DNA. It was found that 4,4a-dihydroxanthone refers to low-toxic compounds.

In order to predict the biological activity of the new derivatives of 4,4a-dihydroxanthone, the PASS (Prediction ofActivity Spectra for Substances) computer program was used. It allows predicting the biological activity spectrum of chemical compounds based on the analysis of structure-activity interrelation. Derivatives of 4,4a-dihydroxanthone were synthesized at the Department of Organic Chemistry of the Saint Petersburg State Chemical Pharmaceutical University. As a result of the screening, it was found that 4,4a-dihydroxanthones can exhibit antibacterial, antifungal, antitumor, and antiviral effects. Antimicrobial activity of the obtained compounds was studied against Gram-positive and Gram-negative bacteria, as well as fungi. Dihydroxanthones were shown to have an inhibitory effect on Gram-positive bacteria. Relationship between the structure of derivatives and their antimicrobial activity is established. The presence of electron-withdrawing substituents led to an increase in activity, and electron-donating substituents reduced the antibacterial effect of the compounds. The most active compound, 5-bromo-7-chloro-4,4a-dihydrox-anthone, was found to be active against certain clinical strains of staphylococci.

The work is devoted to the investigation of colloidal properties of mycelium of Basidiomycetes. In this paper we have investigated the surface properties of Poliporus ciliatus mycelium. Microelectrophoresis and viscometry were selected as research methods. The isoelectric point of the mycelium was defined. Due to increase of particles' size the aqueous dispersion has a high value of the relative viscosity in the pH range from 5,8 to 7,1. In this state the sorption process is the most effective. The predominance of specific sorption of the anionic form of ions was found in the case of buffers, indicating the selectivity of adsorption on the surface of the mycelium.

This is a study of the colloidal properties of mycelia of Basidiomycetes. In this paper we have investigated the surface properties of Abortiporus biennis mycelium. Microelectrophoresis and viscometry were used as research methods. We have determined the optimum pH for the sorption and desorption of substances on the mycelium, and the isoelectric point of the mycelium. In isoelectric state the particle is at maximum compression, sorption of material is the least possible. Maximum sorption on the surface of the mycelium occurs at pH 6,9-7,5 and 6,1-6,5- in the low values of zeta-potential. In case of buffer solutions specific adsorption of anions prevails, indicating the selectivity of sorption on the surface of the mycelium.

This is a study of the colloidal properties of mycelia of Basidiomycetes. In this paper we have investigated the surface properties of Abortiporus biennis mycelium. Microelectrophoresis and viscometry were used as research methods. We have determined the optimum pH for the sorption and desorption of substances on the mycelium, and the isoelectric point of the mycelium. In isoelectric state the particle is at maximum compression, sorption of material is the least possible. Maximum sorption on the surface of the mycelium occurs at pH 6,9-7,5 and 6,1-6,5 in the low values of ζ-potential. In case of buffer solutions specific adsorption of anions prevails, indicating the selectivity of sorption on the surface of the mycelium.

Effect of carbohydrate fractions from mycelium of higher Basidiomycetes Fomes fomentarius and Ganoderma applanatum on Ehrlichs solid tumor growth was investigated. We present evidence, that administration of soluble fraction of Ganoderma applanatum results in significant Ehrlichs solid tumor growth inhibition. In tumor model insoluble fractions had weak antitumor activity. The aqueous extracts have been shown to have a stimulative effect on functional activity of reticuloendothelial system when it was administrated intraperitoneally. However, the soluble fraction had more significant effect on macrophage activation.

Подобраны условия глубинного культивирования базидиомицета Flammulina velutipes (Fr.). P. Karst. Из мицелия гриба выделены растворимая и нерастворимая углеводные фракции в соотношении 1 : 12, содержащие 65.3–84.0% редуцирующих веществ, 7.5–10.0% белка и незначительные минеральные примеси. Основной углеводный компонент мицелия и фракций – глюкоза (53.6% в растворимой и 78.8% в нерастворимой фракции). В растворимой фракции обнаружено высокое содержание маннозы 23.6% и галактозы 18%. Полученные фракции оказывали стимулирующее действие на функциональную активность макрофагов, зрелых клеток системы мононуклеарных фагоцитов – центрального звена клеточного иммунитета, причем растворимая фракция проявляла более выраженный активирующий эффект.

A study is made on a strain of higher basydiomycete Flammulia velutipes (Fr.) P. Karst. The conditions of maximum biomass production by Flammulia velutipes were studied. Soluble and insoluble fractions were isolated from mycelium. The composition of cultured mycelium and aqueous extracts from mycelium were investigated. These objects mainly contained carbohydrates (65.3 and 84.0% in insoluble and soluble fractions, respectively, and 56% mycelium), proteins (7.5–10.0% in fractions and 17.5% in mycelium), as well as an insignificant amount of mineral substances. The main carbohydrate component of fractions was glucose (53.6–78.8%); galactose and mannose were also present, as well as fucose and xylose in insignificant amounts. The aqueous extracts from mycelium demonstrated immunomodulating activity. They rendered a stimulating effect on the functional activity of macrophages—central cells of the reticluoendothelial system. The soluble fraction had a more pronounced effect than the insoluble fraction.

The immunomodulating action of yeast glycans obtained from Rhodotorula rubra (rhonasan) and Sporobolomyces albo-rubescens (heteroglycan Sp-50) was studied under the conditions of experimental endotoxicosis in mice, induced by the injection of the sublethal dose of Escherichia coli lipopolysaccharide (LPS). In endotoxicosis glycans produced a protective effect, depending on the time of injection. The study demonstrated that after the injection of glycans the survival rate of the animals increased and the LPS-inhibited function of peritoneal macrophages and B lymphocytes was completely or partially restored.

It was shown that the yeast polisaccharides such as polyuronides from Bullera tsugae, Sporobolomyces albo-rubescens and mannan sulfate from Rhodotorula rubra (ronasan) stimulated the functional status of macrophages and antibody formation cells. Stimulation effect of polyuronides was more expressed then that of ronasan, but the action of ronasan on the antibody formation was more effective then that of the polyuronides.