I. S. Sazykin

Synthesis and antimicrobial activity of novel structural hybrids of benzofuroxan and benzothiazole derivatives

New compounds containing both benzofuroxan and benzothiazole scaffolds were synthesized through electrophile/nucleophile combination of nitrobenzofuroxan derivatives and 2-mercapto- or 2-aminobenzothiazole derivatives and their biological effect on the natural strain Vibrio genus and different bacterial lux-biosensors was studied. Among all the compounds synthesized, that obtained from 2-mercaptobenzothiazole and 7-chloro-4,6-dinitrobenzofuroxan was toxic for bacterial cells, and also able to activated the 1st type Quorum Sensing system. The reaction between 7-chloro-4,6-dinitrobenzofuroxan and 2-aminobenzothiazole derivatives gave two products, one bearing the benzofuroxan moiety linked to the exocyclic amino nitrogen, and the second derived from the attack of two molecules of electrophile to both the nitrogen atoms of the benzothiazole reagent. Their relative ratio is modifiable by tuning the reagents ratio and the reaction time.

Synthesis, Genotoxicity and UV-protective Activity of New Benzofuroxans Substituted by Aromatic Amines

The synthesis of new organic compounds possessing properties, which can be used for biological or pharmaceutical purpose, is very challenging and is a current trend in heterocyclic chemistry. So benzofuroxans are of great interest from a medical and combinatory chemistry point of view, being effective biologically active compounds. They are easily available, easily tuned and functionalized allowing the creation of databases in which a chemist can find proper informations to prepare the structurally appropriate compound with the requested selective effect. In this work, heterocyclic compounds are prepared on the basis of the interaction of 4,6-dichloro-5-nitrobenzofuroxan with aromatic amines and diamines. Their ability to suppress and prevent genotoxic effects of UV-radiation in the wavelength range between 300-400 nm has been studied. It has been shown that these compounds are able to protect bacterial cells from destructive effects of the UV-radiation. Comparing the results obtained for various benzofuroxans to those obtained for the natural antioxidant  - tocopherol (vitamin E) and for the synthetic antioxidant trolox, which are references in this domain, we have shown that some benzofuroxans quantitatively exhibit a similar protective effect, and that compounds prepared from the reaction between 4,6-dichloro-5-nitrobenzofuroxan and ethylenedianiline possess potent protective potential.

Superoxide Scavenging Activity of Plastoquinone Derivative 10(6 'Plastoquinonyl)decyltriphenylphosphonium (SkQ1)

The plastoquinone derivative 10-(6′-plastoquinonyl)decyltriphenylphosphonium (SkQ1) has the ability to scavenge superoxide anion radical. This ability is manifested both in vitro and in vivo in experiments with the bacterium Escherichia coli. The protective effect of SkQ1 in vivo significantly exceeds that of ascorbic acid.

Expression of SOD and production of reactive oxygen species in Acinetobacter calcoaceticus

Expression of antioxidant enzymes [superoxide dismutase (SOD) and catalase] and generation of reactive oxygen species (ROS) in the presence of various hydrocarbons were investigated in two strains of hydrocarbon-degrading microorganism Acinetobacter calcoaceticus isolated from water (VKPM B-10353) and bottom sediment (EMBM-06). Upon biotransformation of hydrocarbons by the studied strains, superoxide generation strengthening by bacterial cells and accumulation of peroxides in the cultivation medium were observed. The strongest superoxide anion radical generation occurred during the incubation of microorganisms with diesel fuel (increasing 12 times and 2 times), cyclohexane (1.8 times and 1.75 times), a mix of benzene and anthracene (4.4 times and 3.7 times), naphthalene (8 times and 1.9 times) and benz(a)pyrene (2 times and 2.3 times) in strains VKPM B-10353 and EMBM-06 respectively, and anthracene (2.8 times) in strain VKPM B-10353. The accumulation of peroxides in the medium took place upon biotransformation of diesel fuel by both strains. Activity of SOD increased considerably and activity of catalase decreased in cells in the medium with hydrocarbons. Decane and crude oil had the maximum impact on SOD expression. Decane increased SOD expression in strains VKPM B-10353 and EMBM-06 24.4 times and 28.5 times, respectively. Crude oil increased SOD expression in strain VKPM B-10353 19 times, and in strain EMBM-06 16 times. The authors assumed that increased ROS generation and oxidizing stress development in bacteria during the biotransformation of various hydrocarbons can have an adaptive character.

Biosensor-based comparison of the ecotoxicological contamination of the wastewaters of Southern Russia and Southern Germany

To assess the ecotoxicological and sanitary situation in two European metropolis, Rostov-on-Don (Southern Russia) and Munich (Southern Germany), wastewaters of the two cities were examined with a panel of bacterial lux-biosensors: Vibrio aquamarinus VKPM B-11245, Escherichia coli MG1655 (pXen7), E. coli MG1655 (pRecA-lux), E. coli MG1655 (pSoxS-lux), E. coli MG1655 (pKatG-lux), E. coli MG1655 (pIbpA-lux), E. coli MG1655 (GrpE-lux), E. coli MG1655 (pFabA-lux). The presence of different genotoxic compounds and substances with the oxidative and membrane-damaging effects was revealed in contaminated wastewater with the applied panel of the lux-biosensors. The integral toxicity was approximately the same in both cities but demonstrated opposite trends. The presence of genotoxicants and peroxides was higher in the majority of the Munich wastewater samples. There were also differences in the presence of individual toxicants. The presence of the genotoxic compounds might also promote development and dissemination of several antibiotic resistance traits found in microorganisms, a feature more pronounced in Rostov-on-Don wastewaters. By means of polymerase chain reaction assay, antibiotic resistance genes to such antibiotics as ermB, vim and vanB were revealed in two Munich samples. Antibiotic resistance genes were present at all Rostov samples, and genes ndm, vanA, vanB and ermB were found. Taken together, the proposed analytical approach with the application of the constructed panel of biosensors can be applied for monitoring of the ecotoxicological contamination in the wastewaters of large cities.

Synthesis of New ‘Hybrid’ Compounds Based on Benzofuroxans and Aminoalkylnaphthalimides

Pathogenic bacteria and fungi eventually develop resistance to existing drugs, and therefore, we need constant development of new drugs. The research is aimed at addressing fundamental scientific problems—the search for new biologically active compounds among several benzofuroxan‐containing ‘hybrid’ products. N‐substituted naphthalimides were chosen as a second pharmacophore. Benzofuroxanes biological effects were studied by means of bacterial lux‐biosensors. Compounds IIIa, IVa, IIIc, and IVc displayed more expressed bacteriotoxic action in comparison with the initial substances Ia‐c and represent a certain interest for using as antibacterial substances.

Genotoxicity of Don River bottom sediments (2001–2007)

Data on genotoxicity of Don River bottom sediments in 2001–2007 are given. The regions of Lower Don are identified where genotoxin pollution has a chronic character are identified. The possible sources of their input are discussed.

Chemiluminescence analysis of oil oxidizing bacteria Actinetobacter calcoaceticus extracts: Effects of the extracts on pSoxS-lux biosensor

A comparative H2O2-luminol- and Fe(II)-induced chemiluminescence analysis of extracts of two strains of marine oil oxidizing bacteria Actinetobacter calcoaceticus cultivated either in the presence or absence of oil was carried out. Effects of these extracts on E. coli MG1655 biosensor (pSoxS-lux) were studed. Activation of H2O2-induced chemiluminescence in the presence of oil was observed. This suggests activation of free radical lipid peroxidation. Aqueous extracts of microorganisms cultivated in the presence of oil were shown to activate reactive oxygen species production (ROS) in Fe(II)-induced chemiluminescence reaction mixture. Acetone-ethanol extracts induced antioxidative systems of both strains. Chemiluminescence analysis in a biological system carried utilizing E. coli MG1655 (pSoxS-lux) revealed that aqueous extracts of the strains cultivated in the absence of oil contained potential antioxidants.

Erratum to: Expression of SOD and production of reactive oxygen species in Acinetobacter calcoaceticus caused by hydrocarbon oxidation

Expression of antioxidant enzymes [superoxide dismutase (SOD) and catalase] and generation of reactive oxygen species (ROS) in the presence of various hydrocarbons were investigated in two strains of hydrocarbon-degrading microorganism Acinetobacter calcoaceticus isolated from water (VKPM B-10353) and bottom sediment (EMBM-06). Upon biotransformation of hydrocarbons by the studied strains, superoxide generation strengthening by bacterial cells and accumulation of peroxides in the cultivation medium were observed. The strongest superoxide anion radical generation occurred during the incubation of microorganisms with diesel fuel (increasing 12 times and 2 times), cyclohexane (1.8 times and 1.75 times), a mix of benzene and anthracene (4.4 times and 3.7 times), naphthalene (8 times and 1.9 times) and benz(a)pyrene (2 times and 2.3 times) in strains VKPM B-10353 and EMBM-06 respectively, and anthracene (2.8 times) in strain VKPM B-10353. The accumulation of peroxides in the medium took place upon biotransformation of diesel fuel by both strains. Activity of SOD increased considerably and activity of catalase decreased in cells in the medium with hydrocarbons. Decane and crude oil had the maximum impact on SOD expression. Decane increased SOD expression in strains VKPM B-10353 and EMBM-06 24.4 times and 28.5 times, respectively. Crude oil increased SOD expression in strain VKPM B-10353 19 times, and in strain EMBM-06 16 times. The authors assumed that increased ROS generation and oxidizing stress development in bacteria during the biotransformation of various hydrocarbons can have an adaptive character.

The influence of heavy metals, polyaromatic hydrocarbons, and polychlorinated biphenyls pollution on the development of antibiotic resistance in soils

The minireview is devoted to the analysis of the influence of soil pollution with heavy metals, polyaromatic hydrocarbons (PAHs), and the polychlorinated biphenyls (PCBs) on the distribution of antibiotics resistance genes (ARGs) in soil microbiomes. It is shown that the best understanding of ARGs distribution process requires studying the influence of pollutants on this process in natural microbiocenoses. Heavy metals promote co-selection of genes determining resistance to them together with ARGs in the same mobile elements of a bacterial genome, but the majority of studies focus on agricultural soils enriched with ARGs originating from manure. Studying nonagricultural soils would clear mechanisms of ARGs transfer in natural and anthropogenically transformed environments and highlight the role of antibiotic-producing bacteria. PAHs make a considerable shift in soil microbiomes leading to an increase in the number of Actinobacteria which are the source of antibiotics formation and bear multiple ARGs. The soils polluted with PAHs can be a selective medium for bacteria resistant to antibiotics, and the level of ARGs expression is much higher. PCBs are accumulated in soils and significantly alter the specific structure of soil microbiocenoses. In such soils, representatives of the genera Acinetobacter, Pseudomonas, and Alcanivorax dominate, and the ability to degrade PCBs is connected to horizontal gene transfer (HGT) and high level of genomic plasticity. The attention is also focused on the need to study the properties of the soil having an impact on the bioavailability of pollutants and, as a result, on resistome of soil microorganisms.